Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,f...Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.展开更多
Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to ...Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2^(flox/flox)) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.展开更多
Articular cartilage maintains joint homeostasis by adapting to mechanical loading,but both insufficient and excessive loading can impair cartilage integrity.Whether mechanical activity should be restricted in early os...Articular cartilage maintains joint homeostasis by adapting to mechanical loading,but both insufficient and excessive loading can impair cartilage integrity.Whether mechanical activity should be restricted in early osteoarthritis(OA),particularly among exercise enthusiasts,remains controversial.Here,we established in vitro and in vivo models of prolonged moderate mechanical loading(7.5%strain,1 Hz)and analyzed human cartilage from weight-bearing and non-weight-bearing regions using RNA sequencing.Prolonged exposure(≥12 h)significantly increased chondrocyte apoptosis(2.3-fold),reduced expression of the chondrogenic transcription factor SOX9 and the matrix markers COL2A1,and elevated nerve growth factor(NGF)expression(1.8-fold),accompanied by enrichment of neural sensitization and inflammatory pathways.Immunofluorescence staining revealed NGF accumulation in mechanically stressed cartilage.Unlike high-intensity stress,which led to immediate apoptosis,moderate loading induced a delayed pro-apoptotic response after 12 h.These findings indicate that prolonged moderate mechanical loading may promote chondrocyte apoptosis through an NGFmediated inflammatory microenvironment and provide mechanistic evidence suggesting that patients with early OA may benefit from limiting high-impact or prolonged moderate-intensity exercise sessions to prevent cartilage damage and guide rehabilitation.展开更多
Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading a...Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.展开更多
Early knee osteoarthritis(KOA)is characterized by progressive degeneration of the articular cartilage,synovial inflammation,and excessive accumulation of reactive oxygen species(ROS).At present,intra-articular injecti...Early knee osteoarthritis(KOA)is characterized by progressive degeneration of the articular cartilage,synovial inflammation,and excessive accumulation of reactive oxygen species(ROS).At present,intra-articular injection of hyaluronic acid(HA)is widely used to alleviate symptoms;however,its lubrication persistence,antioxidant,and anti-inflammatory abilities are limited,and it is difficult to effectively delay the early process of cartilage degeneration.Based on this,hyaluronic acid-g-lipoic acid(HA-LA)was synthesized by esterification reaction,and HA-LA microspheres were prepared by a reversed-phase emulsion method,which was combined with a macromolecular HA-LA solution to form injectable hydrogels.The objective of this study was to evaluate the efficacy of an injectable hydrogel based on hyaluronic acid-g-lipoic acid microspheres(HA-LA MS)for the treatment of KOA and to verify its injectability,lubricity,reactive oxygen species(ROS)scavenging ability,and anti-inflammatory effects.The results show that the HA-LA MS hydrogel has excellent shear thinning characteristics and continuous injectability,and its microsphere structure significantly reduces the interfacial friction coefficient through the rolling effect.In vitro experiments have shown that the hydrogel can efficiently scavenge ROS,reduce the expression of inflammatory factors,and is non-cytotoxic.The HA-LA MS injectable hydrogel has excellent lubricity,ROS scavenging ability,and anti-inflammatory effects in vivo,which can effectively delay the degeneration of early KOA cartilage,and its efficacy is significantly better than that of traditional hyaluronic acid,making it a promising intra-articular injection preparation.展开更多
BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,c...BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.展开更多
Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from...Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from the Osteoarthritis Initiative(n=3192)were grouped by ST engagement during ages 12–18 years,19–34 years,35–49 years,and 50+years.Participants were categorized as:No ST(no ST at any point;61.7±9.0 years(mean±SD)),Some ST(engaged in ST during 1–3 life stages;58.9±8.7 years),and Lifelong ST(consistently engaged in ST across all life stages;55.6±8.1 years).Measures were collected at baseline and Year 4:Western Ontario and McMaster Universities Osteoarthritis Index Scores(WOMAC;pain,daily activities),Knee Injury and Osteoarthritis Outcome Score(KOOS;sports,recreation),Physical Activity Score for the Elderly(PASE),Short Form-12 Physical Component Score(SF-12 PCS),mobility disability,chair rise time,and walking speed(20 m and 400 m).Results At Year 4,the Lifelong ST group reported better WOMAC activity scores in the right knee along with better WOMAC pain,KOOS sports/recreation,and PASE scores compared to other groups(p<0.05).The Lifelong ST group had the lowest incidence of mobility disability of all groups(0.8%vs.2.3%–4.1%;p=0.015)and maintained the fastest walking speeds in Year 4.Conclusion For those with knee OA,ST throughout life may help preserve function and mobility,allowing for greater physical activity engagement while keeping pain levels relatively lower.展开更多
Knee osteoarthritis(KOA)is a prevalent chronic degenerative joint disorder characterized by an imbalance between articular cartilage degradation and synthesis,a central mechanism in KOA pathogenesis.Given the absence ...Knee osteoarthritis(KOA)is a prevalent chronic degenerative joint disorder characterized by an imbalance between articular cartilage degradation and synthesis,a central mechanism in KOA pathogenesis.Given the absence of disease-modifying therapies,there is a critical need to elucidate the underlying pathological processes,establish reliable biomarkers for early detection and prognosis,and identify safer,more effective therapeutic agents.In recent years,natural products have attracted considerable interest due to their low toxicity,cost-effectiveness,and distinct biological activities,demonstrating significant potential in KOA management.These compounds can impede KOA progression through multiple mechanisms,including promoting cartilage matrix synthesis,mitigating inflammation,reducing oxidative stress,suppressing chondrocyte apoptosis,and modulating autophagy,thereby supporting their translational application.This review summarizes biomarkers relevant to early diagnosis and phenotypic stratification in KOA,with a focus on elucidating the pharmacological actions and molecular mechanisms of natural products,such as flavonoids,alkaloids,saponins,terpenes,and traditional Chinese medicine(TCM)formulas,in KOA intervention,aiming to provide evidence-based strategies for improved disease management.展开更多
The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the...The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the OA meniscus is very important.This study aimed to assess the quasi-static nonlinear mechanical behaviours of the three zones of the OA meniscus by a proposed meso-indentation method,and further to investigate its nonlinear mechanical responses under the stance.Four pairs of menisci were harvested from OA patients during total knee arthroplasty.One pair of the menisci was first used for the histological analysis.Binocular fringe projection technology was then employed to reconstruct the morphology of the other three pairs of the menisci.Subsequently,a meso-indentation method was proposed to characterize the nonlinear behaviors of the meniscus zones,moreover,the hyperelastic model(HEM)together with the Hertz’s elastic model(EM)was used to fit the indentation force-depth curves of the meniscus zones.Furthermore,the fitted HEM and EM materials parameters were used to simulate the mechanical response of the meniscus in the stance by two simplified meniscus models.The results showed that the type Ⅲ collagen widely existed in the OA menisci,and the red-white zone exhibited the best mechanical performance,and the 3-term Mooney-Rivlin model was the best descriptor for the nonlinear mechanical characterization of the three zones.Moreover,the stress or strain distributions of the simplified meniscus models differed significantly between the HEM and EM under the stance,and the EM underestimated the mechanical behaviours of the meniscus.The current work generally provides a novel testing method to study the nonlinear mechanical behaviour of soft biological materials,and is specifically helpful to understand the nonlinear mechanical behaviour of the OA meniscus for which the HEM should be used in the meniscus-related biomechanical studies.展开更多
Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of stan...Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of standardization and uni-formity in current model building methods,which led us to conduct this study.Background:The aim was to investigate the time-and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.Methods:MIA(40,50,and 60 mg/mL)was injected into the left joint of male Sprague-Dawley rats.After 2 weeks,the changes in the KOA rat model were observed by be-havioral evaluation,imaging-level evaluation,and histological-level evaluation.The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.Results:MIA-induced bone surface defects,osteophyte hyperplasia around the artic-ular rim,increased subchondral bone density,thinning of the sparse trabecular bone,structural disorder,and local clustering were observed.The degree of injury gradually increased with the increase in MIA concentration.After 6 weeks,subchondral bone density and sparse trabecular bone increased in the KOA model.Conclusions:The severity of the model also increased significantly with the changes in dose and time.In dose-dependent experiments,this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals.This dose may induce pathological changes stably and is suitable for long-term observation.展开更多
Osteoarthritis(OA)is a degenerative skeletal condition marked by the loss of articular cartilage and changes to subchondral bone homeostasis.Treatments for OA beyond full joint replacement are lacking primarily due to...Osteoarthritis(OA)is a degenerative skeletal condition marked by the loss of articular cartilage and changes to subchondral bone homeostasis.Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease.Mass Spectrometry Imaging(MSI)enables molecular spatial mapping of the proteomic landscape of tissues.Histologic sections of human tibial plateaus from knees of human OA patients and cadaveric controls were treated with collagenase Ⅲ to target extracellular matrix(ECM)proteins prior to MS Imaging of bone and cartilage proteins.Spatial MS imaging of the knee identified distinct areas of joint damage to the subchondral bone underneath areas of lost cartilage.This damaged bone signature extended underneath remaining cartilage in OA joints,indicating subchondral bone remodeling could occur before full thickness cartilage loss in OA.Specific ECM peptide markers from OA-affected medial tibial plateaus were compared to their healthier lateral halves from the same patient,as well as to healthy,age-matched cadaveric knees.Overall,31 peptide candidates from ECM proteins,including Collagen alpha-1(Ⅰ),Collagen alpha-1(Ⅲ),and surprisingly,Collagen alpha-1(Ⅵ)and Collagen alpha-3(Ⅵ),exhibited significantly elevated abundance in diseased tissues.Additionally,highly specific hydroxyproline-containing collagen peptides,mainly from collagen typeⅠ,dominated OA subchondral bone directly under regions of lost cartilage but not areas where cartilage remained intact.A separate analysis of synovial fluid from a second cohort of OA patients found similar regulation of collagens and ECM proteins via LC-MS/MS demonstrating that markers of subchondral bone remodeling discovered by MALDI-MS may be detectable as biomarkers in biofluid samples.The identification of specific protein markers for subchondral bone remodeling in OA advances our molecular understanding of disease progression in OA and provides potential new biomarkers for OA detection and disease grading.展开更多
BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neu...BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.展开更多
BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favo...BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favoured,reverse TSA(RTSA)is increasingly utilized.AIM To systematically compare the outcomes of RTSA and TSA in this specific patient population.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.Retrospective comparative studies evaluating RTSA and TSA in patients with GHOA and intact rotator cuff were included.Key outcomes assessed included complication and reoperation rates,patient-reported outcome measures(PROMs),and range of motion.Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool.RESULTS Twelve studies encompassing 1608 patients(580 RTSA,1028 TSA)met inclusion criteria.RTSA was associated with a lower reoperation rate compared to TSA[odds ratio=0.37;95%confidence interval(CI):0.14-0.94;P value=0.04],while no significant difference in overall complication rates was observed(odds ratio=0.47;95%CI:0.19-1.16;P value=0.10).RTSA patients showed superior outcomes in University of California Los Angeles,Simple Shoulder Test,and Shoulder Pain and Disability Index scores;however,the differences did not exceed the minimal clinically important difference.TSA patients had significantly better external rotation(mean difference=-9.0°;95%CI:-13.21 to-5.02;P value<0.0001).No significant differences were found in other range of motion measures or satisfaction scores.The overall methodological quality of included studies was moderate to serious.CONCLUSION In patients with GHOA and an intact rotator cuff,RTSA may offer comparable or improved outcomes to TSA with lower reoperation rates and similar complication profiles.Functional outcomes favour RTSA in certain patientreported outcome measures,while TSA retains an advantage in external rotation.Surgical decision-making should remain individualized based on patient characteristics and functional demands.展开更多
Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to...Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to joint function loss and disability.Signal transducer and activator of transcription 3(STAT3)up-regulates the expression of MMP-13,which degrades collagen Ⅱ.Our previous study found that 5,7,3',4'-tetramethoxyflavone(TMF)exhibited protective effects on OA chondrocytes.This study aims to investigate the protective role of TMF in inhibiting ECM degradation by mediating the Sirt1/STAT3 signaling pathway.Methods:Rat OA models were established by the injection of monosodium iodoacetate(MIA).Hematoxylin&eosin(HE)staining and immunohistochemistry(IHC)analysis were performed.IL-1β stimulated C28/I2 cells were used as OA-like chondrocyte cell model.Western blotting assays were used to determine the protein expression.Results:The expression of MMP-13 was upregulated while type Ⅱ collagen expression is downregulated,and the phosphorylation level of STAT3 is increased in rat OA models.TMF reverses the STAT3-mediated expression of MMP-13 and type v collagen.Activation of STAT3 or inhibition of Sirt1 function attenuates the inhibitory effect of TMF on ECM degradation.Conclusion:TMF can inhibit ECM degradation mediated by the STAT3 signal pathway by activating Sirt1 expression in OA cell and animal models.展开更多
Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elu...Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.展开更多
OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patient...OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kellgren-Lawrence gradeⅡ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chinese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous electrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,including rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had continuous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tissue-bone management.展开更多
Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,ha...Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.展开更多
Osteoarthritis(OA)is a degenerative joint disease with significant clinical and societal impact.Traditional diagnostic methods,including subjective clinical assessments and imaging techniques such as X-rays and MRIs,a...Osteoarthritis(OA)is a degenerative joint disease with significant clinical and societal impact.Traditional diagnostic methods,including subjective clinical assessments and imaging techniques such as X-rays and MRIs,are often limited in their ability to detect early-stage OA or capture subtle joint changes.These limitations result in delayed diagnoses and inconsistent outcomes.Additionally,the analysis of omics data is challenged by the complexity and high dimensionality of biological datasets,making it difficult to identify key molecular mechanisms and biomarkers.Recent advancements in artificial intelligence(AI)offer transformative potential to address these challenges.This review systematically explores the integration of AI into OA research,focusing on applications such as AI-driven early screening and risk prediction from electronic health records(EHR),automated grading and morphological analysis of imaging data,and biomarker discovery through multi-omics integration.By consolidating progress across clinical,imaging,and omics domains,this review provides a comprehensive perspective on how AI is reshaping OA research.The findings have the potential to drive innovations in personalized medicine and targeted interventions,addressing longstanding challenges in OA diagnosis and management.展开更多
BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clin...BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.展开更多
Osteoarthritis(OA)is the most prevalent joint disease and icariin is a promising drug for its treatment.However,the clinical use of icariin is hindered by poor water solubility,low bioavailability,and nonspecific rele...Osteoarthritis(OA)is the most prevalent joint disease and icariin is a promising drug for its treatment.However,the clinical use of icariin is hindered by poor water solubility,low bioavailability,and nonspecific release and biological distribution.Herein,sulfonated azocalix[4]arene(SAC4A)with enhanced water solubility,recognition capacity,and designed responsiveness was used to improve the efficiency of icariin for OA therapy.SAC4A,a macrocycle with well-defined molecular weight and structure,could encapsulate and enhance water solubility of various drugs.In addition,SAC4A enables hypoxia-responsive release of loaded drug.Compared with icariin treatment,supramolecular complex icariin@SAC4A significantly relieved OA symptoms of rats,including more regular bone morphology and structure,and lower degree of cartilage damage.Moreover,the supramolecular formulation demonstrated various advantages,including easy preparation,hypoxia-triggered release,and small size that conducive to drug penetration.展开更多
文摘Kiehl and colleagues1 utilized data from the Osteoarthritis Initiative(OAI)to address a clinically significant question:Is lifetime participation in strength training(ST)associated with improved trajectories of pain,function,and mobility in individuals with knee osteoarthritis(OA)?Among 3192 participants,those classified as“Lifelong ST”(n=142)demonstrated superior 4-year patient-reported outcomes and exhibited the lowest incidence of mobility disability(0.8%vs 2.3%–4.1%).Notably,they also maintained the fastest walking speeds at Year 4.
基金supported by an NIH grant R01 DE031413 (M.V.B.)。
文摘Temporomandibular joint osteoarthritis(TMJ-OA) affects a significant proportion of the population worldwide.However,there has been no substantial progress in the development of FDA-approved drugs for treatment due to a lack of understanding of the specific factors regulating key TMJ-OA molecular mechanisms.Lysyl Oxidase-Like-2(LOXL2) promotes knee joint cartilage protection and is down regulated in a TMJ-OA animal model.We evaluated the role of LOXL2 in TMJ cartilage,its molecular mechanism,and gene networks using in vivo Loxl2 knockout mice(Acan-Cre;Loxl2^(flox/flox)) and ex vivo goat TMJ cartilage.Our results show that Loxl2 knockout in mouse cartilage upregulates Il1b,Mmp9,Mmp13,Adamts4,and Adamts5,but reduces the levels of aggrecan and proteoglycan.Loxl2 deleted TMJ cartilage show a higher enrichment of inflammatory response,TNFA signaling via NF-κB,extracellular matrix(ECM),and collagen degradation pathway network.Conversely,LOXL2 treatment reduces interleukin-1beta(IL-1β)-induced expression of Mmp13,protects mitochondrial function,and ECM from degeneration.Importantly,LOXL2attenuates IL-1 β-induced chondrocyte apoptosis via the phosphorylation of NF-κB and expression of the pain-related gene PTGS2(encodes COX2).Taken together,Loxl2 knockout mice exacerbate TMJ-OA through cartilage/ECM degradation,mitochondrial dysfunction,chondrocyte apoptosis,and inflammatory gene expression,whereas LOXL2 treatment mitigate these effects.
基金supported by the Zhejiang Medical and Health Innovation Talent Support Project(Grant No.2021RC128 to S.S.)Zhejiang Medicine and Health Science and Technology Project(2025KY1540 to J.J.L.)+3 种基金Zhejiang Province Health Science and Technology Project(2024KY409 and 2021KY1086 to J.Y.L.)Huzhou Science and Technology Planning Project(2020GY10 to W.L.,2022GZ65 to J.Y.L.)Huzhou Basic and Clinical Translation of Orthopedics Key Laboratory(Grant No.HZGKSYS01Y to S.S.)South Taihu Lake Outstanding Young Health Talents Cultivation Program(Grant No.rsk2023001 to S.S.).
文摘Articular cartilage maintains joint homeostasis by adapting to mechanical loading,but both insufficient and excessive loading can impair cartilage integrity.Whether mechanical activity should be restricted in early osteoarthritis(OA),particularly among exercise enthusiasts,remains controversial.Here,we established in vitro and in vivo models of prolonged moderate mechanical loading(7.5%strain,1 Hz)and analyzed human cartilage from weight-bearing and non-weight-bearing regions using RNA sequencing.Prolonged exposure(≥12 h)significantly increased chondrocyte apoptosis(2.3-fold),reduced expression of the chondrogenic transcription factor SOX9 and the matrix markers COL2A1,and elevated nerve growth factor(NGF)expression(1.8-fold),accompanied by enrichment of neural sensitization and inflammatory pathways.Immunofluorescence staining revealed NGF accumulation in mechanically stressed cartilage.Unlike high-intensity stress,which led to immediate apoptosis,moderate loading induced a delayed pro-apoptotic response after 12 h.These findings indicate that prolonged moderate mechanical loading may promote chondrocyte apoptosis through an NGFmediated inflammatory microenvironment and provide mechanistic evidence suggesting that patients with early OA may benefit from limiting high-impact or prolonged moderate-intensity exercise sessions to prevent cartilage damage and guide rehabilitation.
文摘Osteoarthritis(OA) and rheumatoid arthritis(RA) have long been framed as degenerative and autoimmune entities, respectively;mounting evidence instead supports a unified mechano-immune paradigm in which joint loading and inflammatory signaling are reciprocally reinforcing. In this review, we synthesize advances across mechanotransduction(Piezo1;YAP/TAZ), focaladhesion/cytoskeletal regulation(vinculin, filamin-A;upstream talin-1/Kindlin-2/paxillin), and niche inflammatory mediators(HE4, IL-36/IL-38) to explain how mechanical stress and cytokines co-produce persistent catabolism, synovial invasion, and fibrotic remodeling. We articulate a dual-hit model in which OA is predominantly mechanical-overload-driven, with secondary inflammation, whereas RA is immune-driven but imposes abnormal mechanical stress that further distorts joint biomechanics;both converge on canonical hubs(NF-κB/MAPK/JAK-STAT) to accelerate matrix degradation and apoptosis. Building on this framework, we propose integrated multi-marker panels that combine mechanosensors and adhesion proteins with conventional assays(CRP, ESR, anti-CCP) to enhance differential diagnosis and prognostication, particularly in postmenopausal women, where estrogen decline heightens mechano-immune susceptibility, thereby offering a means to quantify the impact of mechano-immune dysregulation. Integrating mechanotransductive and cytoskeletal biomarkers with conventional serological indices has been reported to improve differential diagnosis between osteoarthritis and rheumatoid arthritis in exploratory studies. While the magnitude of diagnostic gain varies across cohorts, combined biomarker strategies generally show enhanced discriminatory performance compared with single-marker approaches. These findings highlight translational potential but require validation in large, standardized clinical populations before routine implementation. Finally, we map translational opportunities spanning Piezo1 inhibition(GsMTx4), YAP/TAZ blockade(verteporfin), IL-36 axis antagonism(IL-36Ra, IL-38), anti-HE4 strategies for RA-ILD, and adhesion-stabilizing approaches, alongside mechanoresponsive biomaterials for regenerative applications and precision medicine guided by biomarker profiles. Collectively, this review reframes OA and RA as mechano-immune syndromes and delineates a clinically actionable roadmap from biophysics to bedside.
基金financially supported by the National Natural Science Foundation of China(Nos.82272472 and 52373146)。
文摘Early knee osteoarthritis(KOA)is characterized by progressive degeneration of the articular cartilage,synovial inflammation,and excessive accumulation of reactive oxygen species(ROS).At present,intra-articular injection of hyaluronic acid(HA)is widely used to alleviate symptoms;however,its lubrication persistence,antioxidant,and anti-inflammatory abilities are limited,and it is difficult to effectively delay the early process of cartilage degeneration.Based on this,hyaluronic acid-g-lipoic acid(HA-LA)was synthesized by esterification reaction,and HA-LA microspheres were prepared by a reversed-phase emulsion method,which was combined with a macromolecular HA-LA solution to form injectable hydrogels.The objective of this study was to evaluate the efficacy of an injectable hydrogel based on hyaluronic acid-g-lipoic acid microspheres(HA-LA MS)for the treatment of KOA and to verify its injectability,lubricity,reactive oxygen species(ROS)scavenging ability,and anti-inflammatory effects.The results show that the HA-LA MS hydrogel has excellent shear thinning characteristics and continuous injectability,and its microsphere structure significantly reduces the interfacial friction coefficient through the rolling effect.In vitro experiments have shown that the hydrogel can efficiently scavenge ROS,reduce the expression of inflammatory factors,and is non-cytotoxic.The HA-LA MS injectable hydrogel has excellent lubricity,ROS scavenging ability,and anti-inflammatory effects in vivo,which can effectively delay the degeneration of early KOA cartilage,and its efficacy is significantly better than that of traditional hyaluronic acid,making it a promising intra-articular injection preparation.
文摘BACKGROUND Knee osteoarthritis(KOA),a common disabling pathology characterized by knee joint pain,swelling,and functional impairment,primarily affects middle-aged and older adults.In addition to physical limitations,chronic pain often leads to psychological problems,including anxiety and depression,which further impact patients’quality of life.AIM To examine the efficacy and safety of celecoxib plus duloxetine in managing chronic pain,anxiety,and depression in patients with KOA.METHODS A retrospective analysis was conducted on 123 patients with KOA treated at our center between February 2020 and February 2023.Of these,66 received celecoxib plus duloxetine,and 57 received celecoxib alone.Outcomes were assessed using the Visual Analog Scale(VAS),the Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC),and the Self-Rating Anxiety Scales(SAS)/Self-Rating Depression Scales(SDS).Safety was evaluated by monitoring changes in liver function enzymes(alanine aminotransferase,aspartate aminotransferase),creatinine,and blood urea nitrogen.RESULTS Patients receiving celecoxib plus duloxetine showed significantly greater reductions in VAS and WOMAC and greater improvements in SAS and SDS scores compared with those receiving celecoxib alone.Hepatorenal function did not differ significantly between the treatment groups.Logistic regression analysis identified patient age,educational background,and treatment regimen as independent predictors of inadequate improvement in negative emotional symptoms.CONCLUSION In patients with KOA,celecoxib plus duloxetine effectively mitigates chronic pain and improves anxiety and depressive symptoms without increasing adverse hepatic or renal effects.These findings support its use as a safe and effective treatment option.
文摘Background This study compared knee osteoarthritis(OA)outcomes specific to pain,physical function,and quality of life in later life based on strength training(ST)participation over a lifetime.Methods Participants from the Osteoarthritis Initiative(n=3192)were grouped by ST engagement during ages 12–18 years,19–34 years,35–49 years,and 50+years.Participants were categorized as:No ST(no ST at any point;61.7±9.0 years(mean±SD)),Some ST(engaged in ST during 1–3 life stages;58.9±8.7 years),and Lifelong ST(consistently engaged in ST across all life stages;55.6±8.1 years).Measures were collected at baseline and Year 4:Western Ontario and McMaster Universities Osteoarthritis Index Scores(WOMAC;pain,daily activities),Knee Injury and Osteoarthritis Outcome Score(KOOS;sports,recreation),Physical Activity Score for the Elderly(PASE),Short Form-12 Physical Component Score(SF-12 PCS),mobility disability,chair rise time,and walking speed(20 m and 400 m).Results At Year 4,the Lifelong ST group reported better WOMAC activity scores in the right knee along with better WOMAC pain,KOOS sports/recreation,and PASE scores compared to other groups(p<0.05).The Lifelong ST group had the lowest incidence of mobility disability of all groups(0.8%vs.2.3%–4.1%;p=0.015)and maintained the fastest walking speeds in Year 4.Conclusion For those with knee OA,ST throughout life may help preserve function and mobility,allowing for greater physical activity engagement while keeping pain levels relatively lower.
基金supported by the National Science Foundation of China(No.82474144)the Zhejiang Province Technological Leading Talents Fund Project(No.2022R52031)。
文摘Knee osteoarthritis(KOA)is a prevalent chronic degenerative joint disorder characterized by an imbalance between articular cartilage degradation and synthesis,a central mechanism in KOA pathogenesis.Given the absence of disease-modifying therapies,there is a critical need to elucidate the underlying pathological processes,establish reliable biomarkers for early detection and prognosis,and identify safer,more effective therapeutic agents.In recent years,natural products have attracted considerable interest due to their low toxicity,cost-effectiveness,and distinct biological activities,demonstrating significant potential in KOA management.These compounds can impede KOA progression through multiple mechanisms,including promoting cartilage matrix synthesis,mitigating inflammation,reducing oxidative stress,suppressing chondrocyte apoptosis,and modulating autophagy,thereby supporting their translational application.This review summarizes biomarkers relevant to early diagnosis and phenotypic stratification in KOA,with a focus on elucidating the pharmacological actions and molecular mechanisms of natural products,such as flavonoids,alkaloids,saponins,terpenes,and traditional Chinese medicine(TCM)formulas,in KOA intervention,aiming to provide evidence-based strategies for improved disease management.
基金supported by the National Nature Science Foundation of China(Grant Nos.32171307,12372307,12172089,61821002 and 82102567)the Basic Research Plan Natural Science Foundation of Jiangsu Province(Grant No.BK20232023)+1 种基金the Nature Science Foundation of Jiangsu Province(Grant No.BK20200144)the Postgraduate Research and Practice Innovation Program of Jiangsu Province(Grant No.5007032303).
文摘The meniscus plays an important role in the biomechanical function of the knee joint,but knee osteoarthritis(OA)deteriorates the mechanical properties of the meniscus.Thus understanding the mechanical behaviour of the OA meniscus is very important.This study aimed to assess the quasi-static nonlinear mechanical behaviours of the three zones of the OA meniscus by a proposed meso-indentation method,and further to investigate its nonlinear mechanical responses under the stance.Four pairs of menisci were harvested from OA patients during total knee arthroplasty.One pair of the menisci was first used for the histological analysis.Binocular fringe projection technology was then employed to reconstruct the morphology of the other three pairs of the menisci.Subsequently,a meso-indentation method was proposed to characterize the nonlinear behaviors of the meniscus zones,moreover,the hyperelastic model(HEM)together with the Hertz’s elastic model(EM)was used to fit the indentation force-depth curves of the meniscus zones.Furthermore,the fitted HEM and EM materials parameters were used to simulate the mechanical response of the meniscus in the stance by two simplified meniscus models.The results showed that the type Ⅲ collagen widely existed in the OA menisci,and the red-white zone exhibited the best mechanical performance,and the 3-term Mooney-Rivlin model was the best descriptor for the nonlinear mechanical characterization of the three zones.Moreover,the stress or strain distributions of the simplified meniscus models differed significantly between the HEM and EM under the stance,and the EM underestimated the mechanical behaviours of the meniscus.The current work generally provides a novel testing method to study the nonlinear mechanical behaviour of soft biological materials,and is specifically helpful to understand the nonlinear mechanical behaviour of the OA meniscus for which the HEM should be used in the meniscus-related biomechanical studies.
基金Construction Project of High-Level Traditional Chinese Medicine Key Discipline of National Administration of Traditional Chinese Medicine,Grant/Award Number:zyyzdxk-2023022Key Team of Scientific and Technological Innovation Talents of Shanxi Province with Integrated Traditional Chinese and Western Medicine for Preventing and Treating Rheumatological Diseases,Grant/Award Number:202204051002033+4 种基金Traditional Chinese Medicine+Stem Cell Innovation Project,Grant/Award Number:2024KJZY0062023 Shanxi Graduate Research Practice Project,Grant/Award Number:2023KY6762023 Graduate Innovation and Entrepreneurship Project of Shanxi University of Traditional Chinese Medicine,Grant/Award Number:2023CX023 and 2023CX027Science and Technology Innovation Project for University in Shanxi Province,Grant/Award Number:2022L358Key Laboratory of Rheumatological and Immunological Diseases Treated by Integrated Chinese and Western Medicine,Grant/Award Number:zyyyjs2024021。
文摘Knee osteoarthritis(KOA)is a chronic degenerative disease.Monosodium iodoac-etate(MIA)induction is the most commonly used therapeutic effect evaluation and mechanism of action research model;we observed a lack of standardization and uni-formity in current model building methods,which led us to conduct this study.Background:The aim was to investigate the time-and dose-related changes in the behavioral and pathological characteristics in the MIA-induced KOA model rat.Methods:MIA(40,50,and 60 mg/mL)was injected into the left joint of male Sprague-Dawley rats.After 2 weeks,the changes in the KOA rat model were observed by be-havioral evaluation,imaging-level evaluation,and histological-level evaluation.The changes were also compared after 40-mg/mL MIA injection for 2 and 6 weeks.Results:MIA-induced bone surface defects,osteophyte hyperplasia around the artic-ular rim,increased subchondral bone density,thinning of the sparse trabecular bone,structural disorder,and local clustering were observed.The degree of injury gradually increased with the increase in MIA concentration.After 6 weeks,subchondral bone density and sparse trabecular bone increased in the KOA model.Conclusions:The severity of the model also increased significantly with the changes in dose and time.In dose-dependent experiments,this study revealed that 40 mg/mL was the optimal dose to induce significant pathological changes without causing undue discomfort or death in animals.This dose may induce pathological changes stably and is suitable for long-term observation.
文摘Osteoarthritis(OA)is a degenerative skeletal condition marked by the loss of articular cartilage and changes to subchondral bone homeostasis.Treatments for OA beyond full joint replacement are lacking primarily due to gaps in molecular knowledge of the biological drivers of disease.Mass Spectrometry Imaging(MSI)enables molecular spatial mapping of the proteomic landscape of tissues.Histologic sections of human tibial plateaus from knees of human OA patients and cadaveric controls were treated with collagenase Ⅲ to target extracellular matrix(ECM)proteins prior to MS Imaging of bone and cartilage proteins.Spatial MS imaging of the knee identified distinct areas of joint damage to the subchondral bone underneath areas of lost cartilage.This damaged bone signature extended underneath remaining cartilage in OA joints,indicating subchondral bone remodeling could occur before full thickness cartilage loss in OA.Specific ECM peptide markers from OA-affected medial tibial plateaus were compared to their healthier lateral halves from the same patient,as well as to healthy,age-matched cadaveric knees.Overall,31 peptide candidates from ECM proteins,including Collagen alpha-1(Ⅰ),Collagen alpha-1(Ⅲ),and surprisingly,Collagen alpha-1(Ⅵ)and Collagen alpha-3(Ⅵ),exhibited significantly elevated abundance in diseased tissues.Additionally,highly specific hydroxyproline-containing collagen peptides,mainly from collagen typeⅠ,dominated OA subchondral bone directly under regions of lost cartilage but not areas where cartilage remained intact.A separate analysis of synovial fluid from a second cohort of OA patients found similar regulation of collagens and ECM proteins via LC-MS/MS demonstrating that markers of subchondral bone remodeling discovered by MALDI-MS may be detectable as biomarkers in biofluid samples.The identification of specific protein markers for subchondral bone remodeling in OA advances our molecular understanding of disease progression in OA and provides potential new biomarkers for OA detection and disease grading.
基金Supported by the Central Guided Local Science and Technology Development Fund Project for Science and Technology Innovation Base Construction,No.Guike ZY24212046National Natural Science Foundation of China,No.U22A2092+3 种基金Guangxi Education Science“the 14th Five-Year Plan”2024 Special Project“Research on Steam Education Practice in Rehabilitation Engineering”,No.2024ZJY304the Research Basic Ability Enhancement Program for Young and Middle-aged Teachers of Guangxi,No.2025KY2255the Innovation Project of GUET Graduate Education,No.2025YCXB010Natural Science Research Project of Guilin Life and Health Career Technical College,No.2025GKKY04.
文摘BACKGROUND The therapeutic role of neurodynamic mobilization in improving lower limb function in patients with mild post-traumatic knee osteoarthritis remains poorly understood.AIM To further elucidate the role of neurodynamic mobilization in facilitating knee joint functional recovery.METHODS Thirty-two patients with post-traumatic knee osteoarthritis treated at Chonghua Hospital of Traditional Chinese Medicine(Guilin)from March 2024 to August 2025 were randomly assigned to a control group(n=16)or an intervention group(n=16).Both groups received eight weeks of conventional treatment;and the intervention group additionally underwent neurodynamic mobilization.Outcomes including pain assessed by the visual analogue scale,active range of motion,Lysholm score,stork stand test,single hop test,and Y-balance test were assessed before and after the intervention.RESULTS There were no significant differences between the two groups in baseline characteristics,including gender,age,body mass index,or surgical side(P>0.05).Two-way repeated-measures analysis of variance demonstrated significant time×group interaction effects for the visual analogue scale score(F=13.364,P<0.05),Lysholm knee score(F=20.385,P<0.05),stork stand test(F=103.756,P<0.05),and Y-balance test score(F=8.089,P<0.05).CONCLUSION Neurodynamic mobilization effectively reduces pain,improves knee function,and enhances lower limb balance in patients with mild post-traumatic knee osteoarthritis.
文摘BACKGROUND The optimal surgical approach for patients with primary glenohumeral osteoarthritis(GHOA)and an intact rotator cuff remains debated.While anatomic total shoulder arthroplasty(TSA)has traditionally been favoured,reverse TSA(RTSA)is increasingly utilized.AIM To systematically compare the outcomes of RTSA and TSA in this specific patient population.METHODS A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines.Retrospective comparative studies evaluating RTSA and TSA in patients with GHOA and intact rotator cuff were included.Key outcomes assessed included complication and reoperation rates,patient-reported outcome measures(PROMs),and range of motion.Risk of bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions tool.RESULTS Twelve studies encompassing 1608 patients(580 RTSA,1028 TSA)met inclusion criteria.RTSA was associated with a lower reoperation rate compared to TSA[odds ratio=0.37;95%confidence interval(CI):0.14-0.94;P value=0.04],while no significant difference in overall complication rates was observed(odds ratio=0.47;95%CI:0.19-1.16;P value=0.10).RTSA patients showed superior outcomes in University of California Los Angeles,Simple Shoulder Test,and Shoulder Pain and Disability Index scores;however,the differences did not exceed the minimal clinically important difference.TSA patients had significantly better external rotation(mean difference=-9.0°;95%CI:-13.21 to-5.02;P value<0.0001).No significant differences were found in other range of motion measures or satisfaction scores.The overall methodological quality of included studies was moderate to serious.CONCLUSION In patients with GHOA and an intact rotator cuff,RTSA may offer comparable or improved outcomes to TSA with lower reoperation rates and similar complication profiles.Functional outcomes favour RTSA in certain patientreported outcome measures,while TSA retains an advantage in external rotation.Surgical decision-making should remain individualized based on patient characteristics and functional demands.
基金Project Supported by Jiangxi Provincial Natural Science Foundation(20212ACB206002)。
文摘Objective:Osteoarthritis(OA)is a degenerative joint disease characterized by extracellular matrix(ECM)degradation,chondrocyte apoptosis,and chronic inflammation.Cartilage destruction and ECM degeneration contribute to joint function loss and disability.Signal transducer and activator of transcription 3(STAT3)up-regulates the expression of MMP-13,which degrades collagen Ⅱ.Our previous study found that 5,7,3',4'-tetramethoxyflavone(TMF)exhibited protective effects on OA chondrocytes.This study aims to investigate the protective role of TMF in inhibiting ECM degradation by mediating the Sirt1/STAT3 signaling pathway.Methods:Rat OA models were established by the injection of monosodium iodoacetate(MIA).Hematoxylin&eosin(HE)staining and immunohistochemistry(IHC)analysis were performed.IL-1β stimulated C28/I2 cells were used as OA-like chondrocyte cell model.Western blotting assays were used to determine the protein expression.Results:The expression of MMP-13 was upregulated while type Ⅱ collagen expression is downregulated,and the phosphorylation level of STAT3 is increased in rat OA models.TMF reverses the STAT3-mediated expression of MMP-13 and type v collagen.Activation of STAT3 or inhibition of Sirt1 function attenuates the inhibitory effect of TMF on ECM degradation.Conclusion:TMF can inhibit ECM degradation mediated by the STAT3 signal pathway by activating Sirt1 expression in OA cell and animal models.
基金supported by the Anhui Provincial Natural Science Foundation(Grant No.2308085MH250)the Natural Science Research Project of Anhui Educational Committee(Grant No.2023AH053327)the Scientific Research Fund Project of Anhui Medical University(2020xkj039).
文摘Chondrocyte senescence is a critical pathological hallmark of osteoarthritis(OA).Aberrant mechanical stress is considered a pivotal determinant in chondrocyte aging;however,the precise underlying mechanism remains elusive.Our findings demonstrate that SPI1 plays a significant role in counteracting chondrocyte senescence and inhibiting OA progression.SPI1 binds to the PERK promoter,thereby promoting its transcriptional activity.Importantly,PERK,rather than GCN2,facilitates eIF2αphosphorylation,activating the mitochondrial unfolded protein response(UPRmt)and impeding chondrocyte senescence.Deficiency of SPI1 in mechanical overload-induced mice leads to diminished UPRmt activation and accelerated OA progression.Intra-articular injection of adenovirus vectors overexpressing SPI1 and PERK effectively mitigates cartilage degeneration.In summary,our study elucidates the crucial regulatory role of SPI1 in the pathogenesis of chondrocyte senescence by activating UPRmt signaling through PERK,which may present a novel therapeutic target for treating OA.
文摘OBJECTIVE To investigate the intervention effects of tissue-bone homeostasis manipulation(TBHM)on peripatellar biomechanical parameters and knee joint function in knee osteoarthritis(KOA)patients.METHODS Sixty patients with KOA(Kellgren-Lawrence gradeⅡ-Ⅲ)were recruited from the Acupuncture-Moxibustion Rehabilitation Department,Anhui University of Chinese Medicine between October 2024 and May 2025.Participants were randomized into a TBHM group(n=30)or a transcutaneous electrical neuromuscular stimulation(TENS)group(n=30).Using two-way repeated measures ANOVA,biomechanical indicators,including rectus femoris tension,vastus medialis tension,vastus lateralis tension,patellar ligament tension,lateral patellar displacement(LPD),medial patellar displacement(MPD),normalized patellar mobility(LPD/patellar width[PW],MPD/PW),knee flexion range of motion,and functional indicators,including KOOS subscales,time up and go test(TUGT),were compared between groups at baseline and after 6 weeks of intervention.RESULTS After intervention,all biomechanical and knee joint function indicators in the TBHM group were significantly improved(P<0.05,P<0.01),while only the vastus medialis tension,TUGT and KOOS Pain,ADL and QoL scores in the control group were significantly improved(P<0.01).The improvement amplitudes of biomechanical indicators in the TBHM group,including rectus femoris tension,vastus lateralis tension,patellar ligament tension,MPD/PW,LPD/PW and knee flexion range of motion were better than those in the control group(P<0.05,P<0.01).In the functional evaluation,the interaction effects of the TBHM group in all dimensions of the KOOS score and TUGT were statistically significant(P<0.05,P<0.01).Post-hoc simple effect analysis confirmed that there were significant differences in the above indicators between the two groups after intervention(P<0.05),and all indicators showed a significant main effect of time(P<0.01),suggesting that the intervention measures had continuous and cumulative curative effects.CONCLUSION TBHM effectively improves joint function and quality of life in KOA patients by restoring dynamic equilibrium in soft tissue tension and patellar mobility,ultimately achieving the therapeutic goal of concurrent tissue-bone management.
文摘Knee osteoarthritis(OA)is a debilitating condition with limited long-term treatment options.The therapeutic potential of mesenchymal stem cells(MSCs),particularly those derived from bone marrow aspirate concentrate,has garnered attention for cartilage repair in OA.While the iliac crest is the traditional site for bone marrow harvesting(BMH),associated morbidity has prompted the exploration of alternative sites such as the proximal tibia,distal femur,and proximal humerus.This paper reviews the impact of different harvesting sites on mesenchymal stem cell(MSC)yield,viability,and regenerative potential,emphasizing their relevance in knee OA treatment.The iliac crest consistently offers the highest MSC yield,but alternative sites within the surgical field of knee procedures offer comparable MSC characteristics with reduced morbidity.The integration of harvesting techniques into existing knee surgeries,such as total knee arthroplasty,provides a less invasive approach while maintaining thera-peutic efficacy.However,variability in MSC yield from these alternative sites underscores the need for further research to standardize techniques and optimize clinical outcomes.Future directions include large-scale comparative studies,advanced characterization of MSCs,and the development of personalized harvesting strategies.Ultimately,the findings suggest that optimizing the site of BMH can significantly influence the quality of MSC-based therapies for knee OA,enhancing their clinical utility and patient outcomes.
基金supported by the National Natural Science Foundation of China(82302757)Shenzhen Science and Technology Program(JCY20240813145204006,SGDX20201103095600002,JCYJ20220818103417037,KJZD20230923115200002)+1 种基金Shenzhen Key Laboratory of Digital Surgical Printing Project(ZDSYS201707311542415)Shenzhen Development and Reform Program(XMHT20220106001).
文摘Osteoarthritis(OA)is a degenerative joint disease with significant clinical and societal impact.Traditional diagnostic methods,including subjective clinical assessments and imaging techniques such as X-rays and MRIs,are often limited in their ability to detect early-stage OA or capture subtle joint changes.These limitations result in delayed diagnoses and inconsistent outcomes.Additionally,the analysis of omics data is challenged by the complexity and high dimensionality of biological datasets,making it difficult to identify key molecular mechanisms and biomarkers.Recent advancements in artificial intelligence(AI)offer transformative potential to address these challenges.This review systematically explores the integration of AI into OA research,focusing on applications such as AI-driven early screening and risk prediction from electronic health records(EHR),automated grading and morphological analysis of imaging data,and biomarker discovery through multi-omics integration.By consolidating progress across clinical,imaging,and omics domains,this review provides a comprehensive perspective on how AI is reshaping OA research.The findings have the potential to drive innovations in personalized medicine and targeted interventions,addressing longstanding challenges in OA diagnosis and management.
文摘BACKGROUND Oral treatment of glucosamine(GA) combined with chondroitin sulfate(CS) was reportedly effective for pain relief and function improvement in osteoarthritis patients with moderate to severe knee pain in clinical trials. While the effectiveness of GA and CS on both clinical and radiological findings has been demonstrated, only a few high-quality trials exist. Therefore, controversy regarding their effectiveness in real-world clinical practice remains.AIM To investigate the impact of GA + CS on clinical outcomes of patients with knee and hip osteoarthritis in routine clinical practice.METHODS A multicenter prospective observational cohort study included 1102 patients of both genders with knee or hip osteoarthritis(Kellgren & Lawrence grades Ⅰ-Ⅲ) in 51 clinical centers in the Russian Federation from November 20, 2017, to March 20,2020, who had started to receive oral capsules of glucosamine hydrochloride 500 mg and CS 400mg according to the approved patient information leaflet starting from 3 capsules daily for 3 wk,followed by a reduced dosage of 2 capsules daily before study inclusion(minimal recommended treatment duration is 3-6 mo). Changes in subscale scores [Pain, Symptoms, Function, and Quality of Life(QOL)] of the Knee Injury and Osteoarthritis Outcome Score(KOOS)/Hip Disability and Osteoarthritis Outcome Score(HOOS) questionnaires during the observational period(up to 54-64wk with a total of 4 visits). Patients’ treatment satisfaction, data on the combined oral use of glucosamine hydrochloride and CS, concomitant use of non-steroidal anti-inflammatory drugs(NSAIDs), and adverse events(AEs) were also evaluated.RESULTS A total of 1102 patients with knee and hip osteoarthritis were included in the study. The mean patient age was 60.4 years, most patients were women(87.8%), and their average body mass index was 29.49 kg/m2. All subscale scores(Pain, Symptoms, Function, and QOL) of the KOOS and HOOS demonstrated clinically and statistically significant improvements. In patients with knee osteoarthritis, the mean score increases from baseline to the end of Week 64 were 22.87, 20.78,16.60, and 24.87 on Pain, Symptoms, Physical Function(KOOS-PS), and QOL subscales(P < 0.001for all), respectively. In patients with hip osteoarthritis, the mean score increases were 22.81, 19.93,18.77, and 22.71 on Pain, Symptoms, Physical Function(HOOS-PS), and QOL subscales(P < 0.001for all), respectively. The number of patients using any NSAIDs decreased from 43.1% to 13.5%(P < 0.001) at the end of the observation period. Treatment-related AEs occurred in 2.8% of the patients and mainly included gastrointestinal disorders [25 AEs in 24(2.2%) patients]. Most patients(78.1%) were satisfied with the treatment.CONCLUSION Long-term oral GA + CS was associated with decreased pain, reduced concomitant NSAID therapy, improved joint function and QOL in patients with knee and hip osteoarthritis in routine clinical practice.
基金supported by grants from the National Natural Science Foundation of China(Nos.82374489,U20A20259 and 22201299)the Scientific Research Program of the Tianjin Municipal Education Commission(No.2021ZD013)。
文摘Osteoarthritis(OA)is the most prevalent joint disease and icariin is a promising drug for its treatment.However,the clinical use of icariin is hindered by poor water solubility,low bioavailability,and nonspecific release and biological distribution.Herein,sulfonated azocalix[4]arene(SAC4A)with enhanced water solubility,recognition capacity,and designed responsiveness was used to improve the efficiency of icariin for OA therapy.SAC4A,a macrocycle with well-defined molecular weight and structure,could encapsulate and enhance water solubility of various drugs.In addition,SAC4A enables hypoxia-responsive release of loaded drug.Compared with icariin treatment,supramolecular complex icariin@SAC4A significantly relieved OA symptoms of rats,including more regular bone morphology and structure,and lower degree of cartilage damage.Moreover,the supramolecular formulation demonstrated various advantages,including easy preparation,hypoxia-triggered release,and small size that conducive to drug penetration.
