BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clin...Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.展开更多
Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidit...Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.展开更多
Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation...Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.展开更多
Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant i...Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.展开更多
Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective a...Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.展开更多
Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury...Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.展开更多
BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bo...BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.展开更多
Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone home...Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone homeostasis,promoting osteoclastogenesis and the accumulation of senescent cells.In line with updated cancer hallmarks,senescent mesenchymal stem/stromal cells(MSCs),osteoblasts,and osteocytes contribute to remodeling of the BM microenvironment,thereby favoring pre-metastatic niche(PMN)formation and subsequent bone metastasis.We previously demonstrated that untreated stage III-B breast cancer patients(BCPs)exhibit increased oxidative stress and elevated reactive oxygen species(ROS)levels,accompanied by senescent and functionally impaired BM-MSCs—key regulators of BM/bone homeostasis.In the present study,we sought to identify the molecular targets affected by oxidative stress that drive MSC senescence in these patients.Methods:BM-MSCs were isolated from untreated stage III-B BCPs and healthy volunteers(HVs).Oxidative stress responses were evaluated by quantitative real-time PCR(qRT-PCR)analysis of stress-and antioxidant-related genes.Oxidative damage to DNA,proteins,and lipids was assessed using alkaline comet assay,chromosomal aberration(CAs)analysis,micronuclei(MN)and nuclear blebs(NBs)quantification,protein carbonyl content,and detection of 4-hydroxynonenal(4-HNE)adducts.The MSC secretome was analyzed by label-free quantitative proteomics followed by Gene Ontology enrichment analysis.Results:Our results show that elevated oxidative stress in BCPs induces the overexpression of oxidative stress-related and antioxidant response genes in BM-MSCs;however,this response is insufficient to prevent extensive ROS-induced damage to deoxyribonucleic acid(DNA),proteins,and lipids.In addition,proteomic analysis of the BM-MSC secretome revealed a distinct protein expression profile in BCPs compared with HVs.Conclusions:Together,these findings highlight oxidative stress-induced MSC damage as a key mechanism contributing to PMN formation and suggest potential therapeutic targets to mitigate bone metastasis in advanced breast cancer.展开更多
Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue en...Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.展开更多
BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.A...BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.展开更多
The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the orig...The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.展开更多
Phosphorus plays an indispensable role in the food chain,yet phosphorus mineral resources are finite,underscoring the urgency for developing a closed-loop phosphorus economy.Although there have been advances in phosph...Phosphorus plays an indispensable role in the food chain,yet phosphorus mineral resources are finite,underscoring the urgency for developing a closed-loop phosphorus economy.Although there have been advances in phosphorus recovery from various waste materials,modern agriculture still depends on adequate phosphorus supply to support plant growth.In this study,we explored the amorphization of Ox bone using phytic acid(OxPA),and investigated how varying treatment durations influence the resulting structure.Inductively Coupled Plasma(ICP)analysis was employed to quantify phosphate solubilization.Additionally,pot experiments were conducted to assess the phosphate efficiency of Ox-PA in comparison to untreated Ox bone and control group.The results showed that Ox-PA exhibited significantly higher phosphate solubilization(2973 ppm)than untreated counterpart(13 ppm).When used as a fertilizer,Ox-PA markedly enhanced both aboveground and belowground biomass and root development in maize plants.Moreover,it facilitated increased phosphorus uptake by the plants during their early growth stages.These findings indicate that Ox-PA not only holds significant potential for promoting agronomic sustainability but also contributes meaningfully to the establishment of a circular phosphorus economy.展开更多
Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)rel...Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)relies on barrier membranes,predominantly from animals or synthetic materials,to improve osteogenesis by avoiding undesired soft tissue cells from defect sites.In this study,membranes were prepared from zein,a corn-derived protein,using a simple extraction and casting method,followed by optional formaldehyde cross-linking to evaluate their behavior for application in GBR.The membranes were characterised by FTIR,DSC,TGA,tensile strength analysis,and in vitro biological assays.Cross-linked membranes exhibited improved mechanical strength(~5 MPa)and slower degradation(~43%mass loss over 30 days),while non-cross-linked membranes disintegrated more rapidly.Cytotoxicity assays using GM07492 fibroblasts confirmed biocompatibility,and cell migration studies demonstrated effective barrier function.These results indicated that zein membranes,particularly in their cross-linked form,combine biodegradability,mechanical integrity,and cellular safety,suggesting significant potential as sustainable GBR materials.This work introduces,for the first time,zein membranes prepared from corn crude extract for GBR in dentistry,paving the way for eco-friendly alternatives to animal-derived products.展开更多
Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological b...Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.展开更多
Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relativ...Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.展开更多
Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and ...Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.展开更多
Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains uncle...Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.展开更多
The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized...The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.展开更多
Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that ...Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing.A unique Il4ra^(+)Ccl2^(high) neutrophil subset drove intense postinjury TRPV1^(+)nociceptive ingrowth,which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4(LXA4)in osteoblasts.Mechanistically,osteoblastic autophagy activated by nociceptor-derived calcitonin gene-related peptide(CGRP)suppressed the nuclear translocation of arachidonate 5-lipoxygenase(5-LOX)to favor the LXA4 biosynthesis.Moreover,in alveolar bone from patients with Type Ⅱ diabetes,we found diminished nociceptive innervation correlated with reduced autophagy,increased inflammation,and impaired bone formation.Activating nociceptive nerves by spicy diet or topical administration of a clinical-approved TRPV1 agonist showed therapeutic benefits on alveolar bone healing in diabetic mice.These results reveal a critical neuroimmune interaction underlying the inflammation-regeneration balance during bone repairing and may lead to novel therapeutic strategies for inflammatory bone diseases.展开更多
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
文摘Bone Research is an open access,fully peer-reviewed journal publishing the foremost progress and novel understanding of all aspects of bone science.The journal highlights the breakthrough discoveries in basic and clinical aspects of bone biology,pathophysiology and regeneration,as well as other significant findings related to bone.
基金performed as part of the cmRNAbone project funded by the European Union’s Horizon 2020 research and innovation program under the Grant Agreement No 874790。
文摘Bone fractures represent a significant global healthcare burden.Although fractures typically heal on their own,some fail to regenerate properly,leading to nonunion,a condition that causes prolonged disability,morbidity,and mortality.The challenge of treating nonunion fractures is further complicated in patients with underlying bone disorders where systemic and local factors impair bone healing.Traditional treatment approaches,including autografts,allografts,xenografts,and synthetic biomaterials,face limitations such as donor site pain,immune rejection,and insufficient mechanical strength,underscoring the need for alternative strategies.Biologic therapies have emerged as promising tools to enhance bone regeneration by leveraging the body’s natural healing processes.This review explores the critical role of conventional and emerging biologics in fracture healing.We categorize biologic therapies into protein-based treatments,gene and transcript therapies,small molecules,peptides,and cell-based therapies,highlighting their mechanisms of action,advantages,and clinical relevance.Finally,we examine the potential applications of biologics in treating fractures associated with bone disorders such as osteoporosis,osteogenesis imperfecta,rickets,osteomalacia,Paget’s disease,and bone tumors.By integrating biologic therapies with existing biomaterial-based strategies,these innovative approaches have the potential to transform clinical management and improve outcomes for patients with difficult-to-heal fractures.
基金supported by grant provided by the Sao Paulo Research Foundation-FAPESP.Grant#2023/15750-7。
文摘Bone resorption is a vital physiological process that enables skeletal remodeling,maintenance,and adaptation to mechanical forces throughout life.While tightly regulated under the physiological state,its dysregulation contributes to pathological conditions such as osteoporosis,rheumatoid arthritis,and periodontitis.Periodontitis is a highly prevalent chronic inflammatory disease driven by dysbiotic biofilms that disrupt the oral microbiome,leading to the progressive breakdown of the periodontal ligament,cementum,and alveolar bone and ultimately resulting in tooth loss.This review outlines the molecular and cellular mechanisms underlying periodontitis,focusing on osteoclastogenesis,the differentiation and activation of osteoclasts,the primary mediators of bone resorption.Key transcriptional regulators,including NFATc1,c-Fos,and c-Src are discussed alongside major signaling pathways such as Mitogen Activated Protein Kinase(MAPK),Janus Tyrosine Kinase/Signal Transducer and Activator of Transcription(JAK/STAT),Nuclear Factor Kappa B(NF-κB),and Phosphoinositide 3-kinase(PI3K)/Akt,to elucidate their roles in the initiation and progression of periodontal bone loss.These pathways orchestrate the inflammatory response and osteoclast activity,underscoring their relevance in periodontitis and other osteolytic conditions.Hallmark features of periodontitis,including chronic inflammation,immune dysregulation,and tissue destruction are highlighted,with emphasis on current and emerging therapeutic strategies targeting these molecular pathways.Special attention is given to small molecules,biologics,and natural compounds that have the potential to modulate key signaling pathways.Although advances in understanding these mechanisms have identified promising therapeutic targets,translation into effective clinical interventions remains challenging.Continued research into regulating bone-resorptive signaling pathways is essential for developing more effective treatments for periodontitis and related inflammatory bone diseases.
文摘Bone regeneration for non-load-bearing defects remains a significant clinical challenge requiring advanced biomaterials and cellular strategies.Adiposederived mesenchymal stem cells(AD-MSCs)have garnered significant interest in bone tissue engineering(BTE)because of their abundant availability,minimally invasive harvesting procedures,and robust differentiation potential into osteogenic lineages.Unlike bone marrow-derived mesenchymal stem cells,AD-MSCs can be easily obtained in large quantities,making them appealing alternatives for therapeutic applications.This review explores hydrogels containing polymers,such as chitosan,collagen,gelatin,and hyaluronic acid,and their composites,tailored for BTE,and emphasizes the importance of these hydrogels as scaffolds for the delivery of AD-MSCs.Various hydrogel fabrication techniques and biocompatibility assessments are discussed,along with innovative modifications to enhance osteogenesis.This review also briefly outlines AD-MSC isolation methods and advanced embedding techniques for precise cell placement,such as direct encapsulation and three-dimensional bioprinting.We discuss the mechanisms of bone regeneration in the AD-MSC-laden hydrogels,including osteoinduction,vascularization,and extracellular matrix remodeling.We also review the preclinical and clinical applications of AD-MSC-hydrogel systems,emphasizing their success and limitations.In this review,we provide a comprehensive overview of AD-MSC-based hydrogel systems to guide the development of effective therapies for bone regeneration.
文摘Objectives:Photodynamic therapy(PDT)is a minimally invasive method used in the treatment of various cancers and skin diseases,but it is not widely used in bone cancer,where the current therapy is often not effective and accompanied by side effects.Alternative and more effective therapies like PDT are needed.In this in-vitro study,the effect of the photosensitizer(PS)chlorin e6(Ce6)on cancerous bone tumor cells using PDT was examined.Methods:A total of 27 tissue specimens from patients with primary bone cancers or bone metastases of different origins were genetically characterized and treated with PDT.Following a 24-h incubation,cell viability was determined,and the effect of PDT on cell migration was analyzed over 48 h.Results:We could demonstrate that the effect on proliferation of PDT in combination with the PS Ce6 was best in cells isolated from primary osteosarcoma and in bone metastases from mammary carcinomas.Besides proliferation,PDT was also effective in inhibiting the migration of these cells.A statistically significant correlation between the PDT effect and CD164 gene expression was detected,indicating that a high expression of this gene could result in a higher effectiveness of the photodynamic treatment.Conclusion:This study analyzes for the first time the effect of PDT in bone cancers and metastases and shows the potential of treating these cancer types with Ce6 PDT.
基金supported by the Key Program of the National Natural Science Foundation of China(32230059)the Basic Science Center Program(T2288102)+3 种基金the Foundation of Frontiers Sciesnce Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the National Natural Science Foundation of China(32401128)the Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251)。
文摘Respiratory inflammatory diseases disrupt bone metabolism and cause pathological bone loss.The lung-bone axis is established in chronic diseases like asthma and cystic fibrosis but is less studied in acute lung injury(ALI),recently implicated in COVID-19-induced bone loss.This study examined the effects of LPS-induced ALI on bone phenotype and explored the role of 2-N,6-O sulfated chitosan(26SCS)in mitigating pneumonia-induced bone loss via inflammatory response modulation.Our findings show that 26SCS effectively reaches bone tissue after oral administration.It promotes macrophage polarization to the M2 phenotype,alleviating immune cascade reactions and inhibiting osteoclast-mediated bone resorption.Increased M2 macrophages support type H vessel formation,enhancing inflammatory bone vascularization.These effects foster a favorable osteogenic microenvironment and mitigate ALI-induced bone loss.While dexamethasone is effective in reducing inflammation,it can aggravate ALI-induced bone loss.Our research offers a therapeutic strategy targeting the lung-bone axis for inflammation-induced bone loss.
文摘BACKGROUND Anterior cruciate ligament(ACL)reconstruction using bone-patellar tendon-bone(BPTB)autografts remains the gold standard for young,active individuals due to its superior biomechanical strength and bone-to-bone healing.However,donor site morbidity,particularly anterior knee pain(AKP),limits its utilization despite its advantages.Various techniques have been proposed to reduce AKP,but they show variable outcomes and several limitations.AIM To assess the incidence and severity of AKP following BPTB ACL reconstruction using an autologous bone grafting technique.METHODS We conducted a retrospective observational study of 24 patients aged 20-45 years,who had primary ACL reconstruction with BPTB grafts.During surgery,autologous cancellous bone generated from tunnel drilling was used to fill the patellar and tibial donor site voids after graft fixation.All patients were followed up for at least twelve months.Using the Kujala Anterior Knee Pain Score,clinical outcomes were evaluated,including the pain-specific subcomponent.RESULTS With scores ranging from 86 to 100,the average overall Kujala score was 95.67±4.01.No patient scored below 85.There was no complication such as patellar fracture,tibial tuberosity fracture,or infection.Grouped data showed 20.8%of patients scored 100,whereas 54.2%scored between 95 and 99,and 25%scored between 86 and 94.One patient(4.2%)had an 8/10 pain subcomponent,whereas 23 patients(95.8%)had a 10/10.CONCLUSION This procedure is easy to incorporate into routine surgical practice,cost-effective and reproducible without requiring extra incisions or raising the patient’s surgical expenses.Excellent short-term results back up this technique.
基金supported by the FONCYT,PICT 2016-#1093,Argentina.CONICET,PIP2014-#300,Argentina.Florencio Fiorini Foundation(#2021-2022),Argentina.
文摘Backgrounds:Breast cancer metastasis remains the leading cause of mortality and frequently targets the bone.Breast cancer cells release soluble factors and extracellular vesicles that disrupt bone marrow(BM)/bone homeostasis,promoting osteoclastogenesis and the accumulation of senescent cells.In line with updated cancer hallmarks,senescent mesenchymal stem/stromal cells(MSCs),osteoblasts,and osteocytes contribute to remodeling of the BM microenvironment,thereby favoring pre-metastatic niche(PMN)formation and subsequent bone metastasis.We previously demonstrated that untreated stage III-B breast cancer patients(BCPs)exhibit increased oxidative stress and elevated reactive oxygen species(ROS)levels,accompanied by senescent and functionally impaired BM-MSCs—key regulators of BM/bone homeostasis.In the present study,we sought to identify the molecular targets affected by oxidative stress that drive MSC senescence in these patients.Methods:BM-MSCs were isolated from untreated stage III-B BCPs and healthy volunteers(HVs).Oxidative stress responses were evaluated by quantitative real-time PCR(qRT-PCR)analysis of stress-and antioxidant-related genes.Oxidative damage to DNA,proteins,and lipids was assessed using alkaline comet assay,chromosomal aberration(CAs)analysis,micronuclei(MN)and nuclear blebs(NBs)quantification,protein carbonyl content,and detection of 4-hydroxynonenal(4-HNE)adducts.The MSC secretome was analyzed by label-free quantitative proteomics followed by Gene Ontology enrichment analysis.Results:Our results show that elevated oxidative stress in BCPs induces the overexpression of oxidative stress-related and antioxidant response genes in BM-MSCs;however,this response is insufficient to prevent extensive ROS-induced damage to deoxyribonucleic acid(DNA),proteins,and lipids.In addition,proteomic analysis of the BM-MSC secretome revealed a distinct protein expression profile in BCPs compared with HVs.Conclusions:Together,these findings highlight oxidative stress-induced MSC damage as a key mechanism contributing to PMN formation and suggest potential therapeutic targets to mitigate bone metastasis in advanced breast cancer.
基金National Key R&D Program of China(grant number 2022YFA1207500)National Natural Science Foundation of China(grant number 82072412).
文摘Treating bone defects complicated by bacterial infections remains a significant clinical challenge.Drawing inspiration from the human body's bone repair mechanisms,the use of biomimetic methods to design tissue engineering scaffolds is of great significance for bone repair.This study synthesized copper(Cu)-doped mesoporous silica nanoparticles(Cu@MSN)modified with hydroxyethyl methacrylate to obtain methacrylated Cu@MSN(Cu@MSNMA).Furtheremore,bio-mimetic nanocomposite hydrogels were prepared by adding Cu@MSNMA to a GelMA/gelatin solution.This hydrogel achieves multi-modal bone tissue biomimicry:(ⅰ)GelMA/gelatin mimics the matrix components in bone ECM,ensuring biocompatibility while promoting cellular behavior(such as adhesion,proliferation,and differentiation);(ⅱ)GelMA/gela-tin and the crosslinking sites introduced by Cu@MSNMA form a stable porous network structure,achieving structural and mechanical biomimicry to provide necessary support for bone defects;(ⅲ)The elemental biomimicry of Si and Cu in Cu@MSNMA achieves efficient osteogenic induction.The effect of different proportions of Cu@MSNMA on the physi-cal properties of the composite hydrogels was investigated to determine the optimal proportion.The results indicated that the mechanical properties of hydrogel were enhanced with the increasing Cu@MSNMA mass ratio.Notably,5%NPs/GelMA/gelatin hydrogel exhibited excellent mechanical property compared to the GelMA/gelatin hydrogel.In vitro and vivo cellular experiments demonstrated a significant enhancement in antibacterial and osteogenic induction with Cu@MSNMA addition.In conclusion,the proposed nanocomposite hydrogel with biomimetic components and ion-regulating properties can serve as a multifunctional scaffold,offering antimicrobial properties for infected bone regeneration,and guide for future research in bone regeneration and three-dimensional printing.
文摘BACKGROUND Esophageal cancer is highly malignant and frequently metastasizes to bones.Concomitant depression worsens prognosis;however,its incidence and determinants in this specific population remain poorly defined.AIM To determine the incidence of depression and its independent risk factors in patients with esophageal cancer and bone metastasis.METHODS A total of 100 consecutive eligible patients admitted between March 2022 and March 2025 were recruited.Depression was assessed with the Beck Depression Inventory-II;scores>4 defined the depression group(n=42)and scores≤4 the non-depression group(n=58).Demographic,clinical,and laboratory variables were compared between the groups.Multivariate logistic regression was used to identify independent risk factors.RESULTS Depression prevalence was 42.0%(42/100).Univariate analysis demonstrated significant differences in monthly per-capita household income,education level,social support,sleep disorders,and serum high-sensitivity C-reactive protein(all P<0.05);no differences were observed in sex,age,tumor characteristics,or other laboratory indices(all P>0.05).Multivariable analysis revealed the following independent risk factors for depression:Low income[odds ratio(OR)=2.66,95%confidence interval(CI):1.17-6.03],low education(OR=2.46,95%CI:1.08-5.61),low social support(OR=5.10,95%CI:1.81-14.39),sleep disorders(OR=2.79,95%CI:1.23-6.35),and elevated high-sensitivity C-reactive protein(OR=1.31 per unit increase,95%CI:1.18-1.46).CONCLUSION Depression is common among patients with esophageal cancer and bone metastasis.Low socioeconomic status,limited education,insufficient social support,sleep disturbances,and systemic inflammation were independent predictors.Interventions that address these modifiable factors may reduce depression risk in this population.
文摘The original online version of this article was revised:The layout update for Article 758 has impacted the page range in the published issue,but did not affect the scholarly content.To ensure consistency with the originally assigned pages(2595-2614),we will need to publish an erratum to correct the article and restore the original page range.The original article has been corrected.
基金supported by the International Partnership Program of Chinese Academy of Sciences[027GJHZ2022033GC]the National Natural Science Foundation of China[22278415 and 52225309]。
文摘Phosphorus plays an indispensable role in the food chain,yet phosphorus mineral resources are finite,underscoring the urgency for developing a closed-loop phosphorus economy.Although there have been advances in phosphorus recovery from various waste materials,modern agriculture still depends on adequate phosphorus supply to support plant growth.In this study,we explored the amorphization of Ox bone using phytic acid(OxPA),and investigated how varying treatment durations influence the resulting structure.Inductively Coupled Plasma(ICP)analysis was employed to quantify phosphate solubilization.Additionally,pot experiments were conducted to assess the phosphate efficiency of Ox-PA in comparison to untreated Ox bone and control group.The results showed that Ox-PA exhibited significantly higher phosphate solubilization(2973 ppm)than untreated counterpart(13 ppm).When used as a fertilizer,Ox-PA markedly enhanced both aboveground and belowground biomass and root development in maize plants.Moreover,it facilitated increased phosphorus uptake by the plants during their early growth stages.These findings indicate that Ox-PA not only holds significant potential for promoting agronomic sustainability but also contributes meaningfully to the establishment of a circular phosphorus economy.
基金funded by São Paulo Research Foundation,FAPESP[research project funding 2019-25318-0 and 2017-18782-6]Conselho Nacional de Desenvolvimento Científico e Tecnológico-CNPq,grant number 305518/2023-2.
文摘Materials from natural sources have been studied to replace the conventional synthetic or animal-derived products as a safer alternative to be used in the healthcare field.In dentistry,guided bone regeneration(GBR)relies on barrier membranes,predominantly from animals or synthetic materials,to improve osteogenesis by avoiding undesired soft tissue cells from defect sites.In this study,membranes were prepared from zein,a corn-derived protein,using a simple extraction and casting method,followed by optional formaldehyde cross-linking to evaluate their behavior for application in GBR.The membranes were characterised by FTIR,DSC,TGA,tensile strength analysis,and in vitro biological assays.Cross-linked membranes exhibited improved mechanical strength(~5 MPa)and slower degradation(~43%mass loss over 30 days),while non-cross-linked membranes disintegrated more rapidly.Cytotoxicity assays using GM07492 fibroblasts confirmed biocompatibility,and cell migration studies demonstrated effective barrier function.These results indicated that zein membranes,particularly in their cross-linked form,combine biodegradability,mechanical integrity,and cellular safety,suggesting significant potential as sustainable GBR materials.This work introduces,for the first time,zein membranes prepared from corn crude extract for GBR in dentistry,paving the way for eco-friendly alternatives to animal-derived products.
文摘Background:Bone tumors represent a significant clinical challenge characterized by high morbidity and complex therapeutic requirements.Although Astragali Radix(Huangqi)is recognized for its potential pharmacological benefits in cancer therapy,the specific molecular mechanisms and their influence on vitamin metabolism pathways in bone malignancies are not well defined.Methods:We conducted an integrated analysis of prognostic genes and survival outcomes in osteosarcoma,focusing on the expression of GPC2 and its correlation with tumor progression and patient survival rates.In order to explore the therapeutic relevance of 20 bioactive compounds extracted from Huangqi,molecular docking was performed to quantify their binding free energies to the GPC2 receptor,shedding light on their potential affinity and biological activity.Furthermore,the expression levels of GPC2 in tumor cells compared to normal cells were analyzed using qRT-PCR.Additionally,the effects of GPC2 overexpression and silencing on cellular viability,apoptotic response,and migratory capacity were systematically investigated.Results:In our study,GPC2 emerged as a significant prognostic gene,where high expression levels correlated with reduced overall survival.The molecular interactions between Astragalus components and the GPC2 receptor reveal compounds with strong affinity,suggesting their potential as effective targets.Furthermore,the overexpression of GPC2 enhanced tumor cell viability and migration,while its knockdown resulted in decreased cell viability and expanded apoptosis.Conclusion:This study demonstrates that Huangqi-derived components may exert anticancer effects by regulating the expression of the GPC2 gene within the vitamin metabolism pathway.These findings offer new insights into the therapeutic potential of traditional herbal medicine for improving bone tumor prognosis and provide a scientific foundation for future translational research.
基金supported by the National Natural Science Foundation of China(No.31800059)。
文摘Osteoporosis is a systemic skeletal disorder characterized by reduced bone mass,compromised bone microstructure,and an increased risk of fractures,primarily due to excessive osteoclast-mediated bone resorption relative to osteoblast-mediated bone formation.While current anti-osteoporosis drugs,such as bisphosphonates and denosumab,predominantly focus on reducing bone resorption,osteoanabolic approaches are essential for restoring bone microarchitecture and ultimately reducing fracture risk.Traditional Chinese medicines(TCMs)and their active ingredients have long been used in China for osteoporosis prevention and treatment.This review provides a comprehensive evaluation of the effects and molecular mechanisms of 65 natural products across 24 categories on osteoblast-mediated bone formation.These compounds promote bone formation by regulating key transcription factors(RUNX2 and Osterix)and signaling pathways,including WNT/β-catenin,bone morphogenic protein(BMP),mitogen-activated protein kinase(MAPK),phosphoinositide 3-kinase/protein kinase B(PI3K/AKT),oxidative stress,autophagy,and epigenetic regulation.Notably,certain natural products[e.g.,icariin(ICA)]exert their effects through multiple targets and pathways.Many of these natural products have demonstrated significant therapeutic efficacy in animal models,such as ovariectomized(OVX)mice.Our findings suggest that natural products with kidney-tonifying,anti-inflammatory,and antioxidant properties,as well as those inhibiting adipocyte differentiation,may hold promise for osteoporosis treatment.Additionally,we highlight current research gaps and propose future directions,including high-throughput screening and validation in diverse animal models,development of novel bone-targeting delivery systems,and identification of natural compounds targeting osteocytes.
基金supported by grants from the National Natural Science Foundation of China(No.82372382,82002333,32371412,and 32071349)the Central Guidance on Local Science and Technology Development Fund of Zhejiang Province(No.2024ZY01033)+1 种基金the Zhejiang Provincial Natural Science Foundation of China(No.LY24C100001)the Key Research and Development Program of Zhejiang(No.2022C01076).
文摘Bone is highly innervated,and its regeneration is significantly nerve-dependent.Extensive evidence suggests that the nervous system plays an active role in bone metabolism and development by modulating osteoblast and osteoclast activity.However,the majority of research to date has focused on the direct effects of peripheral nerves and their neurotransmitters on bone regeneration.Emerging studies have begun to reveal a more intricate role of nerves in regulating the immune microenvironment,which is crucial for bone regeneration.This review summarizes how nerves influence bone regeneration through modulation of the immune microenvironment.We first discuss the changes in peripheral nerves during the regenerative process.We then describe conduction and paracrine pathways through which nerves affect the osteogenic immune microenvironment,emphasizing nerves,neural factors,and their impacts.Our goal is to deepen the understanding of the nerve-immune axis in bone regeneration.A better grasp of how nerves influence the osteogenic immune microenvironment may lead to new strategies that integrate the nervous,immune,and skeletal systems to promote bone regeneration.
基金supported by the National Natural Science Foundation of China (32072936 and 32273080)。
文摘Femoral head necrosis(FHN) is a common leg disorder in the poultry industry often leads to significant cartilage damage.The mechanism behind abnormal apoptosis in FHN broilers,leading to cartilage damage,remains unclear;although endoplasmic reticulum stress(ERS) has been found to play a role in glucocorticoid-induced FHN broilers.In this study,we collected samples from broilers with femoral head separation(FHS) and femoral head separation accompanied with growth plate lacerations(FHSL) in a broiler farm.The aim was to investigate the potential association between the severity of FHN,bone remodeling and cartilage damage.Additionally,primary chondrocytes were treated with methylprednisolone(MP) to construct an in vitro FHN model,followed by inhibition or activation of ERS or hypoxia inducible factor-1α(HIF-1α) to further investigate the mechanism of apoptosis in cartilage.The results suggested that cartilage appeared to be the appropriate tissue to investigate the potential mechanisms of FHN,as the degree of cartilage damage was found to be closely related to the severity of the disease.Bone quality was only affected in FHSL broilers,although factors related to bone metabolism were significantly altered among FHN-affected broilers.In addition,cartilage in FHN-affected broilers exhibited high levels of apoptosis and upregulated expression of ERS-related and HIF-1α,which was consistent with both in vivo and in vitro findings after MP treatment.The results were further supported by treatment with HIF-1α or ERS inhibition or activation.In conclusion,bone remodeling and cartilage homeostasis were affected in FHN broilers,but only cartilage damage was significantly exacerbated with FHN development.Moreover,activation of ERS or HIF-1α resulted in apoptosis in cartilage,thus exhibiting a significant correlation with FHN severity.
基金provided by the Joint Fund for Regional Innovation and Development(U23A20471)Beijing Natural Science Foundation(L242161,L241073,and 7232354)。
文摘The purpose is to explore the effects of Exercise rehabilitation(ER)on bone mineral density(BMD)of the knee,muscle strength(MS),and physical function(PF)after ACL rupture.Finally,A total of 58 patients were randomized into 2 groups(Control Group[CON]:conventional treatment,male=16,female=13,age=[31.63±8.01]years;Exercise rehabilitation group[ER]:6-week ER on CON basis,male=17,female=12,age=[31.26±7.07]years).At baseline and 6 weeks,the knee BMD was measured using DEXA,MS and PF measures were recorded by isokinetic strength test,IKDC,Lysholm,and VAS score.T-tests,analysis of variance(ANOVA),and Mann-Whitney tests were used for comparisons.The BMD outcomes:after a 6-week period,the BMD of the CON([1.47±0.24]g·cm^(-2))was significantly lower than that of the ER([1.65±0.37]g·cm^(-2))at lateral condyle of femur(LCF)(p=0.041).MS outcomes:at 6 weeks,the relative peak torque(RPT)of the quadriceps and hamstrings during concentric contractions in ER group were significantly higher than that in CON group(p<0.001,p=0.017).Similarly,during eccentric contractions in ER group,the RPT of the quadriceps and the H/Q ratio revealed significant variations from the CON group(p=0.033,p=0.043).PF outcomes:the IKDC,Lysholm,and VAS scores of the ER group were significantly improved compared to the CON group(p<0.001,p<0.001,p=0.002).The conclusion is that 6 weeks of ER intervention for patients with ACL rupture can effectively delay the decline of BMD in the LCF of the knee joint,and enhance the restoration of MS and PF.This provides guidance for clinical rehabilitation.
基金The National Natural Science Foundation of China(No.82130027,82301020,82100966)Young Elite Scientists Sponsorship Program by CAST(2024QNRC001)+5 种基金The China Postdoctoral Science Foundation(2023M732283)The National Key Research and Development Program of China(No.2023YFC2413600)The Shanghai Sailing Program(23YF1422000,21YF1424400)Innovative Research Team of High-level Local Universities in Shanghai(SHSMU-ZLCX20212400)Young Elite Scientists Sponsorship Program by CAST(2021QNRC001)Shanghai Pujiang Program(24PJD054).
文摘Nociceptive pain is a cardinal feature of traumatic and inflammatory bone diseases.However,whether and how nociceptors actively regulate the immune response during bone regeneration remains unclear.Here,we found that neutrophil-triggered nociceptive ingrowth functioned as negative feedback regulation to inflammation during bone healing.A unique Il4ra^(+)Ccl2^(high) neutrophil subset drove intense postinjury TRPV1^(+)nociceptive ingrowth,which in return dissipated inflammation by activating the production of pro-resolving mediator lipoxin A4(LXA4)in osteoblasts.Mechanistically,osteoblastic autophagy activated by nociceptor-derived calcitonin gene-related peptide(CGRP)suppressed the nuclear translocation of arachidonate 5-lipoxygenase(5-LOX)to favor the LXA4 biosynthesis.Moreover,in alveolar bone from patients with Type Ⅱ diabetes,we found diminished nociceptive innervation correlated with reduced autophagy,increased inflammation,and impaired bone formation.Activating nociceptive nerves by spicy diet or topical administration of a clinical-approved TRPV1 agonist showed therapeutic benefits on alveolar bone healing in diabetic mice.These results reveal a critical neuroimmune interaction underlying the inflammation-regeneration balance during bone repairing and may lead to novel therapeutic strategies for inflammatory bone diseases.
