Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is la...The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.展开更多
Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indic...Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.展开更多
As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially ...As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.展开更多
Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects w...Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.展开更多
BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical ...BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.展开更多
BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in pati...BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.展开更多
BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes of...BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes offer advantages including reduced donor site morbidity.Our meta-analysis evaluated the comparative efficacy of these approaches across clinical and operative outcomes.AIM To conduct a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.METHODS We conducted a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.Primary outcomes included joint depression,secondary collapse rate,operative time,blood loss,and infection rate.Subgroup analyses were performed by fracture complexity,geographic region,and methodological factors.In addition to that,we also developed a combined outcome score integrating structural,procedural,and complication domains.RESULTS Seven randomized controlled trials with 424 patients(296 bone substitute,128 autograft)were included.No significant differences in joint depression or secondary collapse were observed across fracture complexity categories.Geographic variations were evident,with Western studies showing significantly higher risk of secondary collapse with autografts(risk ratio=1.45,P value=0.02).Both Western and Asian studies have demonstrated significantly reduced blood loss with bone substitutes(70-90 mL less),while operative time reduction was more significant in the Asian studies(23.65 vs 8.00 minutes,P value=0.04 for subgroup difference).The combined outcome score(standardized effect size-0.2481)favored bone substitutes,primarily due to procedural advantages.CONCLUSION Bone substitutes provide similar structural outcomes to autologous bone grafts while having better procedural advantages in tibial plateau fracture management.These findings support bone substitutes as a viable option across fracture patterns.Future studies should focus on specific bone substitute formulations and cost-effectiveness analyses.展开更多
BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-ass...BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.展开更多
Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of...Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.展开更多
The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,...The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.展开更多
Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was dimini...Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.展开更多
The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical ...The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.展开更多
Bone age assessment(BAA)aims to determine whether a child’s growth and development are normal concerning their chronological age.To predict bone age more accurately based on radiographs,and for the left-hand X-ray im...Bone age assessment(BAA)aims to determine whether a child’s growth and development are normal concerning their chronological age.To predict bone age more accurately based on radiographs,and for the left-hand X-ray images of different races model can have better adaptability,we propose a neural network in parallel with the quantitative features from the left-hand bone measurements for BAA.In this study,a lightweight feature extractor(LFE)is designed to obtain the featuremaps fromradiographs,and amodule called attention erasermodule(AEM)is proposed to capture the fine-grained features.Meanwhile,the dimensional information of the metacarpal parts in the radiographs is measured to enhance the model’s generalization capability across images fromdifferent races.Ourmodel is trained and validated on the RSNA,RHPE,and digital hand atlas datasets,which include images from various racial groups.The model achieves a mean absolute error(MAE)of 4.42 months on the RSNA dataset and 15.98 months on the RHPE dataset.Compared to ResNet50,InceptionV3,and several state-of-the-art methods,our proposed method shows statistically significant improvements(p<0.05),with a reduction in MAE by 0.2±0.02 years across different racial datasets.Furthermore,t-tests on the features also confirm the statistical significance of our approach(p<0.05).展开更多
BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of th...BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.展开更多
Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the exte...Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system.Despite the significant advancements in understanding osteoimmunology,the precise role of dendritic cells(DCs)in this field remains under investigation.As key antigen-presenting cells,DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis.Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease,as well as their interaction with skeletal cells in the context of bone repair and regeneration.展开更多
Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs.However,emerging research indicates that bone plays a crucial role in the regulation of sys...Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs.However,emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism.This is achieved through the secretion of a variety of hormones,cytokines,metal ions,extracellular vesicles,and other proteins/peptides,collectively referred to as bone-derived factors(BDFs).BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs,thereby underscoring the profound and concrete implications of bone in human physiology.Nevertheless,there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems.This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo.It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system,circulatory system,glucose and lipid metabolism,central nervous system,urinary system,and reproductive system.The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes.Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.展开更多
Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired b...Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.展开更多
Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through mic...Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.展开更多
The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(B...The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(Becn1),a major regulator of mammalian autophagy,exclusively in the megakaryocytic lineage disrupted autophagy in platelets but did not compromise megakaryopoiesis or the formation and function of platelets.Unexpectedly,conditional Becn1 deletion in male mice led to a remarkable increase in bone mass with improved bone quality,in association with a decrease in sex hormone binding globulin(SHBG)and an increase in free testosterone(FT).In vivo Becn1 overexpression in megakaryocytic lineage-specific cells reduced bone mass and quality,along with an increase in SHBG and a decrease in FT.Transplantation of wild-type bone marrow cells into megakaryocytic lineage Becn1-deficient male mice restored bone mass and normalized SHBG and FT.Furthermore,bilateral orchiectomy of Becn1^(f/f);Pf4-iCre mice,which are crippled with the production of testosterone,resulted in a reduction in bone mass and quality,whereas in vivo overexpression of SHBG,specifically in the liver of Becn1^(f/f);Pf4-iCre mice,decreased FT and reduced bone mass and quality.In addition,metformin treatment,which induces SHBG expression,reduced FT and normalized bone mass in Becn1^(f/f);Pf4-iCre mice.We thus concluded that Becn1 of the megakaryocytic lineage is dispensable locally for platelet hemostasis but limits bone mass by increasing SHBG,which in turn reduces the FT of male mice.Our findings highlight a mechanism by which Becn1 from megakaryocytic lineage cells distally balances bone growth.展开更多
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
文摘The discontinuation of denosumab[antibody targeting receptor activator of nuclear factor kappa B ligand(RANKL)]therapy may increase the risk of multiple vertebral fractures;however,the underlying pathophysiology is largely unknown.In patients who underwent discontinuation after multiple injections of denosumab,the levels of tartrate-resistant acid phosphatase 5b increased compared to pretreatment levels,indicating a phenomenon known as“overshoot.”The rate of decrease in bone mineral density during the withdrawal period was higher than the rate of decrease associated with aging,suggesting that the physiological bone metabolism had broken down.Overshoot and significant bone loss were also observed in mice receiving continuous administration of anti-RANKL antibody after treatment was interrupted,resembling the original pathology.In mice long out of overshoot,bone resorption recovered,but osteoblast numbers and bone formation remained markedly reduced.The bone marrow exhibited a significant reduction in stem cell(SC)antigen 1-and platelet-derived growth factor receptor alpha-expressing osteoblast progenitors(PαS cells)and alkaline phosphatase-positive early osteoblasts.Just before the overshoot phase,the osteoclast precursor cell population expands and RANKL-bearing extracellular vesicles(EVs)became abundant in the serum,leading to robust osteoclastogenesis after cessation of anti-RANKL treatment.Thus,accelerated bone resorption due to the accumulation of RANKLbearing EVs and long-term suppression of bone formation uncoupled from bone resorption leads to the severe bone loss characteristic of denosumab discontinuation.
基金financially supported by the Basic Science Center Program(T2288102)the Key Program of the National Natural Science Foundation of China(32230059)+3 种基金the Foundation of Frontiers Science Center for Materiobiology and Dynamic Chemistry(JKVD1211002)the Project supported by the Young Scientists Fund of the National Natural Science Foundation of China(32401128)Postdoctoral Fellowship Program of CPSF(GZC20230793)Shanghai Post-doctoral Excellence Program(2023251).
文摘Following the discovery of bone as an endocrine organ with systemic influence,bone-brain interaction has emerged as a research hotspot,unveiling complex bidirectional communication between bone and brain.Studies indicate that bone and brain can influence each other’s homeostasis via multiple pathways,yet there is a dearth of systematic reviews in this area.This review comprehensively examines interactions across three key areas:the influence of bone-derived factors on brain function,the effects of brain-related diseases or injuries(BRDI)on bone health,and the concept of skeletal interoception.Additionally,the review discusses innovative approaches in biomaterial design inspired by bone-brain interaction mechanisms,aiming to facilitate bonebrain interactions through materiobiological effects to aid in the treatment of neurodegenerative and bone-related diseases.Notably,the integration of artificial intelligence(AI)in biomaterial design is highlighted,showcasing AI’s role in expediting the formulation of effective and targeted treatment strategies.In conclusion,this review offers vital insights into the mechanisms of bone-brain interaction and suggests advanced approaches to harness these interactions in clinical practice.These insights offer promising avenues for preventing and treating complex diseases impacting the skeleton and brain,underscoring the potential of interdisciplinary approaches in enhancing human health.
基金supported by the National Natural Science Foundation of China(Nos.82160419 and 82302772)Guizhou Basic Research Project(No.ZK[2023]General 201)。
文摘As the global population ages,osteoporotic bone fractures leading to bone defects are increasingly becoming a significant challenge in the field of public health.Treating this disease faces many challenges,especially in the context of an imbalance between osteoblast and osteoclast activities.Therefore,the development of new biomaterials has become the key.This article reviews various design strategies and their advantages and disadvantages for biomaterials aimed at osteoporotic bone defects.Overall,current research progress indicates that innovative design,functionalization,and targeting of materials can significantly enhance bone regeneration under osteoporotic conditions.By comprehensively considering biocompatibility,mechanical properties,and bioactivity,these biomaterials can be further optimized,offering a range of choices and strategies for the repair of osteoporotic bone defects.
基金supported by the National Natural Science Foundation of China(No.82202450).
文摘Large bone defects in load-bearing bone can result from tumor resection,osteomyelitis,trauma,and other factors.Although bone has the intrinsic potential to self-repair and regenerate,the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge.Traditionally,repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites,and autogenous bone grafting remains the“gold standard”treatment.However,the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone,donor-site morbidities,and the risk of rejection.In recent years,the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes.In addition to osteoconductivity and osteoinductivity,optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects,but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength.A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements.In this review,the use of traditional bone grafts in load-bearing bone defects,as well as their advantages and disadvantages,is summarized and reviewed.Furthermore,we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance,structural,and functional bionics to provide ideas and directions for future research.
文摘BACKGROUND Demineralized bone matrix(DBM)is a commonly utilized allogenic bone graft substitute to promote osseous union.However,little is known regarding outcomes following DBM utilization in foot and ankle surgical procedures.AIM To evaluate the clinical and radiographic outcomes following DBM as a biological adjunct in foot and ankle surgical procedures.METHODS During May 2023,the PubMed,EMBASE and Cochrane library databases were systematically reviewed to identify clinical studies examining outcomes following DBM for the management of various foot and ankle pathologies.Data regarding study characteristics,patient demographics,subjective clinical outcomes,radiological outcomes,complications,and failure rates were extracted and analyzed.In addition,the level of evidence(LOE)and quality of evidence(QOE)for each individual study was also assessed.Thirteen studies were included in this review.RESULTS In total,363 patients(397 ankles and feet)received DBM as part of their surgical procedure at a weighted mean follow-up time of 20.8±9.2 months.The most common procedure performed was ankle arthrodesis in 94 patients(25.9%).Other procedures performed included hindfoot fusion,1st metatarsophalangeal joint arthrodesis,5th metatarsal intramedullary screw fixation,hallux valgus correction,osteochondral lesion of the talus repair and unicameral talar cyst resection.The osseous union rate in the ankle and hindfoot arthrodesis cohort,base of the 5th metatarsal cohort,and calcaneal fracture cohort was 85.6%,100%,and 100%,respectively.The weighted mean visual analog scale in the osteochondral lesions of the talus cohort improved from a pre-operative score of 7.6±0.1 to a post-operative score of 0.4±0.1.The overall complication rate was 27.2%,the most common of which was non-union(8.8%).There were 43 failures(10.8%)all of which warranted a further surgical procedure.CONCLUSION This current systematic review demonstrated that the utilization of DBM in foot and ankle surgical procedures led to satisfactory osseous union rates with favorable wound complication rates.Excellent outcomes were observed in patients undergoing fracture fixation augmented with DBM,with mixed evidence supporting the routine use of DBM in fusion procedures of the ankle and hindfoot.However,the low LOE together with the low QOE and significant heterogeneity between the included studies reinforces the need for randomized control trials to be conducted to identify the optimal role of DBM in the setting of foot and ankle surgical procedures.
基金Supported by National Natural Science Foundation of China(General Program),No.82073909Four‘Batches’Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province,No.2023XM022The Shanxi Provincial Central Leading Local Science and Technology Development Fund Project,No.YDZJSX2022A059 and No.YDZJSX20231A059。
文摘BACKGROUND Autonomous cortisol secretion(ACS)is linked to a higher prevalence of metabolic abnormalities and an increased risk of major adverse cardiovascular events.AIM To evaluate glucose and bone metabolism in patients with ACS using a continuous glucose monitoring system(CGMS)and dual-energy X-ray absorptiometry(DXA).METHODS Patients diagnosed with ACS,including Cushing syndrome,mild ACS(MACS),and nonfunctional adrenal incidentaloma(NFAI),were recruited for this study.Glucose variability and glycemic status were assessed using CGMS.Regional bone mineral content(BMC),bone mineral density(BMD),and bone area(BA)were evaluated using DXA.CGMS-and DXA-derived parameters were compared across the subgroups of ACS.Correlation analysis was performed to examine relationships between varying degrees of cortisol secretion,measured by cortisol after 1 mg overnight dexamethasone suppression test(DST)or 24-hour urine free cortisol(24h UFC),and CGMS-or DXA-derived parameters.RESULTS A total of 64 patients with ACS were included in this study:19 with Cushing syndrome,11 with MACS,and 34 with NFAI.Glucose variability,time above range(TAR),and time in range(TIR)along with specific areal BMC,BMD,and BA,differed significantly between groups of Cushing syndrome and NFAI.A significant positive correlation was observed between glucose variability or TAR and cortisol after 1 mg overnight DST or 24h UFC.By contrast,TIR,along with regional BMC,BMD,and BA,were negatively correlated with varying degrees of cortisol secretion.CONCLUSION Glucose and bone metabolism impairments are on a continuum alteration from NFAI to MACS and Cushing syndrome.Prompt attention should be given to these patients with ACS,especially those with mild hormone secretion.Parameters of glucose variability and glycemic status along with bone condition in regions rich in cancellous bone will provide valuable information.
文摘BACKGROUND Tibial plateau fractures often require structural support for metaphyseal defects created during articular reduction.While autologous bone grafting has been utilized as the gold standard,bone substitutes offer advantages including reduced donor site morbidity.Our meta-analysis evaluated the comparative efficacy of these approaches across clinical and operative outcomes.AIM To conduct a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.METHODS We conducted a systematic review and meta-analysis of randomized controlled trials comparing autologous bone grafts with bone substitutes for tibial plateau fractures.Primary outcomes included joint depression,secondary collapse rate,operative time,blood loss,and infection rate.Subgroup analyses were performed by fracture complexity,geographic region,and methodological factors.In addition to that,we also developed a combined outcome score integrating structural,procedural,and complication domains.RESULTS Seven randomized controlled trials with 424 patients(296 bone substitute,128 autograft)were included.No significant differences in joint depression or secondary collapse were observed across fracture complexity categories.Geographic variations were evident,with Western studies showing significantly higher risk of secondary collapse with autografts(risk ratio=1.45,P value=0.02).Both Western and Asian studies have demonstrated significantly reduced blood loss with bone substitutes(70-90 mL less),while operative time reduction was more significant in the Asian studies(23.65 vs 8.00 minutes,P value=0.04 for subgroup difference).The combined outcome score(standardized effect size-0.2481)favored bone substitutes,primarily due to procedural advantages.CONCLUSION Bone substitutes provide similar structural outcomes to autologous bone grafts while having better procedural advantages in tibial plateau fracture management.These findings support bone substitutes as a viable option across fracture patterns.Future studies should focus on specific bone substitute formulations and cost-effectiveness analyses.
基金Supported by the Research Project for Clinical Research on Precision Diagnosis and Innovative Treatment of Bone Marrow Failure,No.2024YFC2510500Jiangsu Provincial Traditional Chinese Medicine Science and Technology Development Plan,No.YB2020102Nantong Municipal Health Commission Research Project,No.QN2023007.
文摘BACKGROUND Thrombotic microangiopathy(TMA)is an acute syndrome characterized by microangiopathic hemolytic anemia,thrombocytopenia,and multi-organ dysfunction due to the microcirculation of platelet thrombi.Cancer-associated TMA is a rare and fatal complication,which often occurs during cancer remission.It is frequently misdiagnosed because of limited clinical awareness.CASE SUMMARY A middle-aged female patient presented to our clinic with a 15-days history of back pain,15 months post-gastrectomy.Cancer-associated TMA was confirmed through bone marrow aspiration,biopsy,and imaging.The patient received intermittent transfusions,fluids,nutrition,and microcirculation therapy with partial coagulation improvement.The family refused intensive care unit admission and plasma exchange,preferring palliative care.The patient died of cerebral hemorrhage and herniation due to disease progression.This case indicates that TMA may serve as an early manifestation of various malignancies,particularly gastric cancer.However,it is often misdiagnosed.Its pathogenesis is not well understood and needs to be further investigated.Currently,no standardized treatment have been developed.Plasma exchange is the only intervention available,though other therapies may also be effective.CONCLUSION In this case of gastric signet-ring cell carcinoma complicated by TMA,the patient achieved transient remission with supportive care but died following treatment discontinuation.Further studies are needed to elucidate the pathological mechanisms and therapeutic strategies for cancer-associated TMA.
基金Supported by Clinical Medical Research Fund of the Zhejiang Medical Association,No.2025ZYC-Z32Henan Provincial Key Research and Development Program,No.231111311000+1 种基金Henan Provincial Science and Technology Research Project,No.232102310411Clinical Medical Research Fund of the Zhejiang Medical Association,2024ZYC-Z30.
文摘Type 2 diabetes markedly elevates fracture risk despite normal or high bone mineral density,a paradox reflecting qualitative skeletal deficits rather than loss of mass.Chronic hyperglycemia fosters the accumulation of advanced glycation end products in bone;their nonenzymatic crosslinks stiffen type I collagen,impair mineralization,and erode mechanical strength.By engaging the receptor for advanced glycation end products,these adducts activate nuclear factorκB and mitogen-activated protein kinase cascades,amplifying oxidative stress,inflammation,osteoblast dysfunction,and osteoclastogenesis.This review synthesizes epidemiological data from type 1 and type 2 diabetes,highlights the limits of densitybased skeletal assessment,and details the molecular pathology of the glycation-collagen axis.It also appraises antiglycation therapies,including formation inhibitors,crosslink breakers and receptor antagonists,with a particular focus on sodium-glucose cotransporter 2 inhibitors that couple glycemic control with modulation of the glycation pathway.By integrating recent basic and clinical advances,we propose a mechanistic framework for diabetic bone disease and outline strategies to mitigate glycationdriven skeletal fragility.
基金supported by National Natural Science Foundation of China(grant numbers 82072523 to Zhiyong Hou)Postdoctoral program of Clinical medicine of Hebei Medical University(grant numbers PD2023012 to Sujuan Xu)+2 种基金Excellent postdoctoral research funding project of Hebei Province(grant numbers B2023005011 to Sujuan Xu)The 16th special grant of China Postdoctoral Science Foundation(grant numbers 2023T160182 to Sujuan Xu)Natural Science Foundation of Hebei Province,China(grant numbers H2023206230 to Yingchao Yin,H2024206186 to Sujuan Xu).
文摘The delicate balance between bone formation by osteoblasts and bone resorption by osteoclasts maintains bone homeostasis.Nuclear receptors(NRs)are now understood to be crucial in bone physiology and pathology.However,the function of the Farnesoid X receptor(FXR),a member of the NR family,in regulating bone homeostasis remains incompletely understood.In this study,in vitro and in vivo models revealed delayed bone development and an osteoporosis phenotype in mice lacking FXR in bone marrow mesenchymal stem cells(BMSCs)and osteoblasts due to impaired osteoblast differentiation.Mechanistically,FXR could stabilize RUNX2 by inhibiting Thoc6-mediated ubiquitination,thereby promoting osteogenic activity in BMSCs.Moreover,activated FXR could directly bind to the Thoc6 promoter,suppressing its expression.The interaction between RUNX2 and Thoc6 was mediated by the Runt domain of RUNX2 and the WD repeat of Thoc6.Additionally,Obeticholic acid(OCA),an orally available FXR agonist,could ameliorate bone loss in an ovariectomy(OVX)-induced osteoporotic mouse model.Taken together,our findings suggest that FXR plays pivotal roles in osteoblast differentiation by regulating RUNX2 stability and that targeting FXR may be a promising therapeutic approach for osteoporosis.
基金supported by grants from National Natural Science Foundation of China(82272444,81972031,81972033)China Postdoctoral Science Foundation(2022M722382)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK-032A)。
文摘Neural EGFL-like 2(NELL2)is a secreted protein known for its regulatory functions in the nervous and reproductive systems,yet its role in bone biology remains unexplored.In this study,we observed that NELL2 was diminished in the bone of aged and ovariectomized(OVX)mice,as well as in the serum of osteopenia and osteoporosis patients.In vitro loss-of-function and gain-offunction studies revealed that NELL2 facilitated osteoblast differentiation and impeded adipocyte differentiation from stromal progenitor cells.In vivo studies further demonstrated that the deletion of NELL2 in preosteoblasts resulted in decreased cancellous bone mass in mice.Mechanistically,NELL2 interacted with the FNI-type domain located at the C-terminus of Fibronectin 1(Fn1).Moreover,we found that NELL2 activated the focal adhesion kinase(FAK)/AKT signaling pathway through Fn1/integrinβ1(ITGB1),leading to the promotion of osteogenesis and the inhibition of adipogenesis.Notably,administration of NELL2-AAV was found to ameliorate bone loss in OVX mice.These findings underscore the significant role of NELL2 in osteoblast differentiation and bone homeostasis,suggesting its potential as a therapeutic target for managing osteoporosis.
基金support of the National Natural Science Foundation of China(Grant No.52205593)Shaanxi Natural Science Foundation Project(2024JC-YBMS-711).
文摘The incidence of large bone defects caused by traumatic injury is increasing worldwide,and the tissue regeneration process requires a long recovery time due to limited self-healing capability.Endogenous bioelectrical phenomena have been well recognized as critical biophysical factors in bone remodeling and regeneration.Inspired by bioelectricity,electrical stimulation has been widely considered an external intervention to induce the osteogenic lineage of cells and enhance the synthesis of the extracellular matrix,thereby accelerating bone regeneration.With ongoing advances in biomaterials and energy-harvesting techniques,electroactive biomaterials and self-powered systems have been considered biomimetic approaches to ensure functional recovery by recapitulating the natural electrophysiological microenvironment of healthy bone tissue.In this review,we first introduce the role of bioelectricity and the endogenous electric field in bone tissue and summarize different techniques to electrically stimulate cells and tissue.Next,we highlight the latest progress in exploring electroactive hybrid biomaterials as well as self-powered systems such as triboelectric and piezoelectric-based nanogenerators and photovoltaic cell-based devices and their implementation in bone tissue engineering.Finally,we emphasize the significance of simulating the target tissue’s electrophysiological microenvironment and propose the opportunities and challenges faced by electroactive hybrid biomaterials and self-powered bioelectronics for bone repair strategies.
基金supported by the grant from the National Natural Science Foundation of China(No.72071019)grant from the Natural Science Foundation of Chongqing(No.cstc2021jcyj-msxmX0185).
文摘Bone age assessment(BAA)aims to determine whether a child’s growth and development are normal concerning their chronological age.To predict bone age more accurately based on radiographs,and for the left-hand X-ray images of different races model can have better adaptability,we propose a neural network in parallel with the quantitative features from the left-hand bone measurements for BAA.In this study,a lightweight feature extractor(LFE)is designed to obtain the featuremaps fromradiographs,and amodule called attention erasermodule(AEM)is proposed to capture the fine-grained features.Meanwhile,the dimensional information of the metacarpal parts in the radiographs is measured to enhance the model’s generalization capability across images fromdifferent races.Ourmodel is trained and validated on the RSNA,RHPE,and digital hand atlas datasets,which include images from various racial groups.The model achieves a mean absolute error(MAE)of 4.42 months on the RSNA dataset and 15.98 months on the RHPE dataset.Compared to ResNet50,InceptionV3,and several state-of-the-art methods,our proposed method shows statistically significant improvements(p<0.05),with a reduction in MAE by 0.2±0.02 years across different racial datasets.Furthermore,t-tests on the features also confirm the statistical significance of our approach(p<0.05).
文摘BACKGROUND The induced-membrane technique was initially described by Masquelet as an effective treatment for large bone defects,especially those caused by infection.Here,we report a case of chronic osteomyelitis of the radius associated with a 9 cm bone defect,which was filled with a large allogeneic cortical bone graft from a bone bank.Complete bony union was achieved after 14 months of follow-up.Previous studies have used autogenous bone as the primary bone source for the Masquelet technique;in our case,the exclusive use of allografts is as successful as the use of autologous bone grafts.With the advent of bone banks,it is possible to obtain an unlimited amount of allograft,and the Masquelet technique may be further improved based on this new way of bone grafting.CASE SUMMARY In this study,we reported a case of repair of a long bone defect in a 40-year-old male patient,which was characterized by the utilization of allograft cortical bone combined with the Masquelet technique for the treatment of the patient's long bone defect in the forearm.The patient's results of functional recovery of the forearm were surprising,which further deepens the scope of application of Masquelet technique and helps to strengthen the efficacy of Masquelet technique in the treatment of long bones indeed.CONCLUSION Allograft cortical bone combined with the Masquelet technique provides a new method of treatment to large bone defect.
基金supported by the“Pioneer and Leading Goose+X”research and development program of Zhejiang Province Science and Technology Department(2024C03193)the National Natural Science Foundation of China(No.82271026)Start-up Fund of Stomatology Hospital,School of Stomatology,Zhejiang University School of Medicine(2023PDF017).
文摘Bone repair and regeneration is a complex spatiotemporal process recruiting a variety of cell types,which need to precisely mediated for effective healing post-damage.The concept of osteoimmunology emphasizes the extensive and intricate crosstalk between the bone and the immune system.Despite the significant advancements in understanding osteoimmunology,the precise role of dendritic cells(DCs)in this field remains under investigation.As key antigen-presenting cells,DCs are critical in orchestrating adaptive immune responses and maintaining tissue homeostasis.Recent researches have further revealed the potential of DCs to influence the development or acceleration of inflammatory and autoimmune bone disease,as well as their interaction with skeletal cells in the context of bone repair and regeneration.
基金supported, in part, by the National Natural Science Foundation of China Grants (82430078, 82261160395, 82230081, 82004395, 82302767)the Shenzhen Medical Research Funds (B2402033, C2401029)+5 种基金the Shenzhen Fundamental Research Program (JCYJ20220818100617036)the National Key Research and Development Program of China Grants (2019YFA0906004)the Guangdong Provincial Science and Technology Innovation Council Grant (2017B030301018)the Shenzhen Key Laboratory of Cell Microenvironment Grant (ZDSYS20140509142721429)the Hubei Provincial Natural Science Foundation of China (2024AFB610)the Science Foundation of Wuhan Union Hospital (2022xhyn032)
文摘Bone has long been acknowledged as a fundamental structural entity that provides support and protection to the body’s organs.However,emerging research indicates that bone plays a crucial role in the regulation of systemic metabolism.This is achieved through the secretion of a variety of hormones,cytokines,metal ions,extracellular vesicles,and other proteins/peptides,collectively referred to as bone-derived factors(BDFs).BDFs act as a medium through which bones can exert targeted regulatory functions upon various organs,thereby underscoring the profound and concrete implications of bone in human physiology.Nevertheless,there remains a pressing need for further investigations to elucidate the underlying mechanisms that inform the effects of bone on other body systems.This review aims to summarize the current findings related to the roles of these significant modulators across different organs and metabolic contexts by regulating critical genes and signaling pathways in vivo.It also addresses their involvement in the pathogenesis of various diseases affecting the musculoskeletal system,circulatory system,glucose and lipid metabolism,central nervous system,urinary system,and reproductive system.The insights gained from this review may contribute to the development of innovative therapeutic strategies through a focused approach to bone secretomes.Continued research into BDFs is expected to enhance our understanding of bone as a multifunctional organ with diverse regulatory roles in human health.
基金financially supported by the National Natural Science Foundation of China(Nos.52103184 and 8226030956)the National Key Research and Development Program of China(No.2022YFC2407503)+3 种基金Key Project of the Natural Science Basic Research Plan of Shaanxi Province(No.2022JZ43)Natural Science Basic Research Program of Shaanxi Province(No.2024JCYBQN-0874)Medical Research Key Project of Xi'an Science and Technology Bureau(No.2024JH-YXZD-0055)Medical Research Project of Xi'an Science and Technology Bureau(No.22YXYJ0083)
文摘Owing to their unique biological effects and physicochemical properties,nanomaterials have garnered substantial attention in the field of bone tissue engineering(BTE),targeting the repair and restoration of impaired bone tissue.In recent years,strategies for the design and optimization of nanomaterials through thiolation modification have been widely applied in BTE.This review concisely summarizes the categories of nanomaterials commonly used in BTE and focuses on various strategies for the modification of nanomaterials via thiolation.A multifaceted analysis of the mechanisms by which thiolated nanomaterials enhance nanomaterial-cell interactions,promote drug loading and release,and modulate osteogenic differentiation is presented.Furthermore,this review introduces biomedical applications of thiolated nanomaterials in BTE,including as scaffold components for bone regeneration,coatings for bone implants,and drug delivery systems.Finally,the future perspectives and challenges in the development of this field are discussed.Thiolation modification strategies provide a platform for developing new ideas and methods for designing nanomaterials for BTE and are expected to accelerate the development and clinical translation of novel bone repair materials.
基金supported by funding from the National Natural Science Foundation of China(82272478,82002330,82202728)the National Key R&D Program of China(No.2022YFF1100100)the Natural Science Foundation of Beijing(L222086).
文摘Systematic bone and muscle loss is a complex metabolic disease,which is frequently linked to gut dysfunction,yet its etiology and treatment remain elusive.While probiotics show promise in managing diseases through microbiome modulation,their therapeutic impact on gut dysfunction-induced bone and muscle loss remains to be elucidated.Employing dextran sulfate sodium(DSS)-induced gut dysfunction model and wide-spectrum antibiotics(ABX)-treated mice model,our study revealed that gut dysfunction instigates muscle and bone loss,accompanied by microbial imbalances.Importantly,Bifidobacterium animalis subsp.lactis A6(B.lactis A6)administration significantly ameliorated muscle and bone loss by modulating gut microbiota composition and enhancing butyrate-producing bacteria.This intervention effectively restored depleted butyrate levels in serum,muscle,and bone tissues caused by gut dysfunction.Furthermore,butyrate supplementation mitigated musculoskeletal loss by repairing the damaged intestinal barrier and enriching beneficial butyrate-producing bacteria.Importantly,butyrate inhibited the NF-κB pathway activation,and reduced the secretion of corresponding inflammatory factors in T cells.Our study highlights the critical role of dysbiosis in gut dysfunction-induced musculoskeletal loss and underscores the therapeutic potential of B.lactis A6.These discoveries offer new microbiome directions for translational and clinical research,providing promising strategies for preventing and managing musculoskeletal diseases.
基金supported in part by grants from the National Natural Science Foundation of China(No.81673093,No.82170227,No.91649113,No.82470165,No.82000121,No.31771640)the Jiangsu Science and Technology Department(No.SBK20200191)+1 种基金the State Key Laboratory of Radiation Medicine and Protection of Soochow University(No.GZC00201)a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions.
文摘The crosstalk between megakaryocytic lineage cells and the skeletal system has just begun to be explored but remains largely elusive.Using conditional gene knockout mouse models,we demonstrated that loss of Beclin 1(Becn1),a major regulator of mammalian autophagy,exclusively in the megakaryocytic lineage disrupted autophagy in platelets but did not compromise megakaryopoiesis or the formation and function of platelets.Unexpectedly,conditional Becn1 deletion in male mice led to a remarkable increase in bone mass with improved bone quality,in association with a decrease in sex hormone binding globulin(SHBG)and an increase in free testosterone(FT).In vivo Becn1 overexpression in megakaryocytic lineage-specific cells reduced bone mass and quality,along with an increase in SHBG and a decrease in FT.Transplantation of wild-type bone marrow cells into megakaryocytic lineage Becn1-deficient male mice restored bone mass and normalized SHBG and FT.Furthermore,bilateral orchiectomy of Becn1^(f/f);Pf4-iCre mice,which are crippled with the production of testosterone,resulted in a reduction in bone mass and quality,whereas in vivo overexpression of SHBG,specifically in the liver of Becn1^(f/f);Pf4-iCre mice,decreased FT and reduced bone mass and quality.In addition,metformin treatment,which induces SHBG expression,reduced FT and normalized bone mass in Becn1^(f/f);Pf4-iCre mice.We thus concluded that Becn1 of the megakaryocytic lineage is dispensable locally for platelet hemostasis but limits bone mass by increasing SHBG,which in turn reduces the FT of male mice.Our findings highlight a mechanism by which Becn1 from megakaryocytic lineage cells distally balances bone growth.
