Bone & Joint Research最新文献

{"title":"Tibial cortex transverse transport accelerates diabetic wound healing via systemic mobilization of non-classical monocytes : an animal study.","authors":"Yongkang Yang, Zhaowei Jiang, Kan Ouyang, Yucong Li, Jian Zhang, Haixing Wang, Shanshan Bai, Sien Lin, Xiaomin Wu, Gang Li, Xiaohua Pan","doi":"10.1302/2046-3758.158.BJR-2025-0377.R1","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0377.R1","url":null,"abstract":"<p><strong>Aims: </strong>To clarify the immunomodulatory mechanisms by which tibial cortex transverse transport (TTT) accelerates wound healing in a type 2 diabetic rat model, with particular focus on the dynamics of subsets of monocytes and macrophages.</p><p><strong>Methods: </strong>A total of 186 male Sprague-Dawley rats were induced as diabetic via a high-fat diet and streptozotocin. A full-thickness skin defect was created on the dorsum of the foot immediately following standard TTT surgery. Wound closure was monitored photographically. At defined timepoints (days 3 to 21), wound tissues underwent histological and immunofluorescence staining (haematoxylin and eosin, Masson's trichrome, picrosirius red, CD68/iNOS/mannose) to assess re-epithelialization, collagen organization, and M1/M2 macrophage populations. Flow cytometry of bone marrow and peripheral blood (CD43 and CD172a markers) quantified classical and non-classical monocyte subsets. Monocyte/macrophage involvement was probed by depleting these cells with clodronate liposomes versus phosphate-buffered saline liposomes.</p><p><strong>Results: </strong>TTT-treated rats achieved complete wound closure by day 21, markedly faster than fixator or sham controls. Histology revealed enhanced re-epithelialization, a thicker epidermis, well-organized type III collagen, and normalized collagen fibre directionality. Immunofluorescence demonstrated a rapid decline in proinflammatory M1 and an increase in reparative M2 macrophages from day 5 onward. Flow cytometry showed a pronounced surge of non-classical monocytes in bone marrow on day 3, followed by elevated circulating levels on days 3 to 6. Monocyte/macrophage depletion markedly delayed healing and disrupted collagen deposition.</p><p><strong>Conclusion: </strong>TTT is associated with accelerated diabetic wound repair, accompanied by preferential mobilization of non-classical monocytes and increased M2 macrophage polarization at the wound site. These findings are consistent with a mechanically induced immunomodulatory process that may contribute to improved healing outcomes.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"937-950"},"PeriodicalIF":5.5,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430152/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148663275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotypic divergence in rotator cuff tear and volumetric muscle loss mouse models following fibroadipogenic progenitor depletion.","authors":"Zili Wang, Luke Sang, Alex Youn, Mengyao Liu, Brian T Feeley, Xuhui Liu","doi":"10.1302/2046-3758.158.BJR-2025-0112.R2","DOIUrl":"10.1302/2046-3758.158.BJR-2025-0112.R2","url":null,"abstract":"<p><strong>Aims: </strong>Fibroadipogenic progenitors (FAPs) are a group of resident muscle stem cells capable of differentiating into fibroblasts and adipocytes, contributing to intramuscular fibrotic and fatty degeneration after injury. However, FAPs are also thought to play a crucial role in muscle regeneration by facilitating satellite cell myogenesis. Despite this dual role, the precise functions of FAPs in muscle degeneration and regeneration remain unclear. This study aimed to utilize a FAP depletion mouse model to define the role of FAPs in two distinct, clinically relevant injury models of rotator cuff tears (RCTs) and tibialis anterior (TA) volumetric muscle loss (VML).</p><p><strong>Methods: </strong>Six PDGFRα-Cre^ERT/DTA mice were applied for fluorescence-activated cell sorting (FACS) evaluation of FAP depletion efficiency with tamoxifen induction. Then, two groups of ten PDGFRα-Cre^ERT/DTA mice and five DTA mice underwent either unilateral supraspinatus and infraspinatus tendons and suprascapular nerve transection (RCT model) or the creation of a 4 mm diameter defect in the unilateral TA (VML model). To induce FAP depletion, tamoxifen or corn oil (control) was administered daily for two weeks before surgery. Gait analysis was conducted at six weeks post-surgery to evaluate shoulder or hindlimb function. Supraspinatus or TA muscles were harvested to assess muscle atrophy and for histological analysis.</p><p><strong>Results: </strong>FACS analysis confirmed a 50% reduction in FAPs following tamoxifen administration in PDGFRα-Cre^ERT/DTA mice. In the RCT model, FAP depletion significantly attenuated muscle atrophy and improved fibrosis, fatty infiltration (FI), and global shoulder function. Conversely, in the VML model, FAP depletion significantly decreased muscle fibrosis but had no effect on FI and functional outcomes.</p><p><strong>Conclusion: </strong>Our results suggest that FAPs play distinct roles in muscle regeneration depending on the specific clinical context. These models can be used to further understand the different injury mechanisms and muscle-specific properties influencing FAP roles in musculoskeletal pathology.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 8","pages":"927-936"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13427427/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148648155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CDK12 mediates the inhibition effect of mechanical unloading on osteoblast proliferation by regulating RNAPII transcription activation.","authors":"Lifang Hu, Wenjin Zhong, Linlin Wang, Shujing Liang, Yunxian Jia, Zixiang Wu, Jingran Shen, Jiajun Sun, Airong Qian","doi":"10.1302/2046-3758.157.BJR-2025-0343.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2025-0343.R1","url":null,"abstract":"<p><strong>Aims: </strong>Mechanical stimuli are crucial in regulating normal osteoblast function to maintain bone homeostasis. Decreased osteoblast proliferation is one of the main causes of osteoporosis induced by mechanical unloading. However, the underlying mechanism remains unclear. Cyclin-dependent kinase 12 (CDK12), a member of the CDK family, plays a key role in regulating cell proliferation. In this study, we aimed to investigate the role of CDK12 in osteoblast proliferation, and its function and underlying mechanism in decreased osteoblast proliferation caused by mechanical unloading.</p><p><strong>Methods: </strong>CDK12 small interfering RNA (siRNA) and CDK12 plasmid were used to knock down and overexpress CDK12 in osteoblasts, respectively. 5-ethynyl-2´-deoxyuridine (EdU) staining, cell counting, and flow cytometry were adopted to detect the effects of mechanical unloading on osteoblast cell proliferation and cell cycle. Immunofluorescence staining was performed to detect the cellular localization of CDK12. Real-time polymerase chain reaction (PCR) and western blot were performed to analyze the expression of CDK12 and downstream molecules.</p><p><strong>Results: </strong>Mechanical unloading significantly reduced the EdU-positive cell ratio and the total cell number of primary osteoblasts, accompanied by a marked decrease of S phase cell percentage. Meanwhile, the expression of CDK12, a key regulator for cell cycle and cell proliferation, was significantly downregulated by mechanical unloading. Loss and gain of function studies revealed that CDK12 knockdown inhibits osteoblast proliferation and S phase cell cycle progression, while CDK12 overexpression increases these parameters. Moreover, mechanical unloading altered the subcellular localization of CDK12, reduced the phosphorylation level of RNA polymerase II (RNAPII), and downregulated the expression of key DNA replication genes, including CDC6, CDT1, ORC2, and TOPBP1. Similar results were obtained in CDK12 knockdown osteoblasts. Furthermore, CDK12 overexpression rescued the decreased osteoblast proliferation and reduced S phase percentage induced by mechanical unloading.</p><p><strong>Conclusion: </strong>The present study demonstrates CDK12 as a critical regulator of osteoblast proliferation under mechanical unloading conditions. Mechanistically, mechanical unloading suppresses osteoblast proliferation by downregulating CDK12 expression, which results in decreased RNAPII phosphorylation and reduced expression of downstream core DNA replication genes. These findings provide a novel mechanistic insight into the inhibitory effects of mechanical unloading on osteoblast proliferation, and reveals CDK12 as a novel potential target for treating disuse osteoporosis.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"914-926"},"PeriodicalIF":5.5,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13391222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148560789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inhibition of Cathepsin C attenuates osteoarthritis by modulating macrophage activated status and reducing tissue inflammatory responses.","authors":"Ye Tian, Xinyue Wang, Xinnan Zhao, Shuang Liu, Xiaohan Yang, Gang Liu, ZhiMing Qi, Lina Guo, JianMei Ma","doi":"10.1302/2046-3758.157.BJR-2025-0222.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2025-0222.R1","url":null,"abstract":"<p><strong>Aims: </strong>Osteoarthritis (OA) is a common degenerative joint disease, with growing evidence suggesting that chronic inflammation plays a critical role in its progression. Targeting chronic inflammation could potentially slow OA development. While Cathepsin C (CatC) has been widely studied in the context of inflammatory diseases, its specific role in OA remains underexplored.</p><p><strong>Methods: </strong>To address this question, we used clinical samples of OA patients and a murine OA model to clarify the expression of CatC and its role in OA. By further isolating and culturing OA-related primary cells, we aimed to identify the source of CatC and determine its impact on various cell types. In addition, we used CatC knockdown mice and specific CatC inhibitors AZD7986 to verify the impact of CatC inhibition on OA progress.</p><p><strong>Results: </strong>Our results demonstrated that CatC expression was significantly upregulated in OA synovium, with infiltrated macrophages playing a crucial role in this upregulation. Furthermore, CatC was identified as a key factor in promoting the release of inflammatory mediators by facilitating the polarization of macrophages towards pro-inflammatory activation state. In turn, macrophage-derived CatC exacerbated inflammation and cartilage degradation through paracrine effects on synovial fibroblasts and chondrocytes. Knockdown of CatC or administration of the specific CatC inhibitor AZD7986 mitigates cartilage damage and synovial inflammation by reducing the expression of inflammatory factors and matrix-degrading enzymes.</p><p><strong>Conclusion: </strong>This study demonstrates that macrophage-derived CatC contributes to OA progression through upregulation of inflammatory mediators and MMP13. These findings suggest that CatC may represent a potential therapeutic target warranting further investigation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"903-913"},"PeriodicalIF":5.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13384741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum.","authors":"Haibo Zhao, Jianbao Gong, Tengbo Yu, Yingze Zhang","doi":"10.1302/2046-3758.157.BJR-2026-00005","DOIUrl":"10.1302/2046-3758.157.BJR-2026-00005","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"891"},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13375383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of impaction energy and bone quality on cementless femoral implant fixation and femoral periprosthetic fracture risk.","authors":"M Abdulhadi Alagha, Rishabh Gupta, Chloe Jordan, Geoffrey Ng, Justin Cobb","doi":"10.1302/2046-3758.157.BJR-2025-0532.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2025-0532.R1","url":null,"abstract":"<p><strong>Aims: </strong>Cementless fixation is the predominant method used in hip arthroplasty worldwide; however, seating implants via impaction remains a balancing act - too much energy may cause fracture, and too little may not seat the implant adequately. Currently, the optimal energy level required for femoral implant fixation is unknown, which adversely affects the variability of long-term implant stability. This study investigated how varying impaction energies affect strain behaviour, fracture risk, and implant fixation in synthetic bone models using cementless femoral implants.</p><p><strong>Methods: </strong>A standardized surgical technique was used to prepare a total of 20 synthetic bone models (Sawbones) - 12 healthy and eight osteoporotic - for femoral impaction. The implants were impacted at three different energy levels (low, medium, and high) using a validated in vitro rig simulator for soft-tissue compliance, with four specimens tested at each velocity and bone type. Strain behaviour and fracture risk, measured as peak strain, were analyzed using digital image correlation with two high-speed cameras. Implant stability was assessed via pull-out fixation tests.</p><p><strong>Results: </strong>Higher impaction energy increased fracture risk but did not significantly increase implant stability. In healthy bone models, mean tensile peak strain was 0.31, 0.69, and 0.97 for low, medium, and high energy strikes, respectively. Osteoporotic models showed the greatest difference between the low and medium energies during the initial two strikes, with peak strains of 0.42 to 0.46 versus 0.79 to 0.84, with subsequent strikes resulting in minimal variation between the two velocities. Implant pull-out forces were similar among the different impaction energy levels within each group (healthy p = 0.10<u>5</u>, osteoporotic p = 0.686), and consistently lower in osteoporotic bones across all energy levels.</p><p><strong>Conclusion: </strong>These biomechanical findings on synthetic bones confirm that multiple lower-energy strikes lead to similar implant fixation outcomes with lower risk of periprosthetic fracture (lower peak strain).</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"892-902"},"PeriodicalIF":5.5,"publicationDate":"2026-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13377574/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148468898","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical study on the 3D morphology and mechanical factors of lumbar facet joints in patients with degenerative lumbar spondylolisthesis.","authors":"Xiao Xiong, Yunsheng Wang, Da Shi, Tong Tong, Baoyue Zhang, Yilai Li, Linfeng Wang","doi":"10.1302/2046-3758.157.BJR-2026-0016.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2026-0016.R1","url":null,"abstract":"<p><strong>Aims: </strong>To construct a mechanical model using a spatial Cartesian coordinate system and vectors, and to explore the role of facet joint morphology and mechanical parameters in degenerative lumbar spondylolisthesis (DLS).</p><p><strong>Methods: </strong>A retrospective imaging study was conducted to collect the demographic data and imaging parameters of patients with and without DLS. The 3D structure and mechanical parameters of facet joint were constructed for comparative analysis. Receiver operating characteristic and regression analysis explore predictors for DLS. A total of 149 patients (67.8% female) were included in the study, with a median age of 63 years (IQR 58.5 to 68.0).</p><p><strong>Results: </strong>Compared with non-DLS patients, there were significant differences in the facet joint angle (FJA), facet degeneration of L4-5, the sagittal joint angle (SJA), and intervertebral angles of L3-5 in DLS. Regardless of correction, the L4-5 posterior shear force of DLS patients is smaller than non-DLS. Posterior shear force has a high area under the curve and is significantly different from FJA, medial shear force, and vertical stress. High SJA and low posterior shear force are independent predictors for the progression of lumbar spondylolisthesis.</p><p><strong>Conclusion: </strong>In addition to the FJA, the larger SJA and lower posterior shear forces are also a good index to predict the progress of DLS. The posterior shear force is a more valuable indicator for predicting DLS progression, and may be a direct factor in the anterior displacement. When the posterior shear force is less than 0.537, the possibility of lumbar spondylolisthesis greatly increases. At this time, even in cases where patients do not experience spondylolisthesis, muscle exercise or intraoperative fixation are recommended to maintain lumbar stability.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"880-890"},"PeriodicalIF":5.5,"publicationDate":"2026-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13372478/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Functionalizing biomaterials for osseointegration - microRNAs at the crossroads of bone formation and immune modulation.","authors":"Mandana Azari, Elena Della Bella, Britt Wildemann","doi":"10.1302/2046-3758.157.BJR-2025-0576.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2025-0576.R1","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) play an important role in post-transcriptional gene regulation by binding to messenger RNA and thereby modulating protein synthesis and affecting cellular functions such as proliferation and apoptosis. In bone biology, miRNAs influence osseointegration, a process vital to the long-term success of orthopaedic implants. This process involves coordinated phases of inflammation, bone formation, and remodelling, which are regulated by miRNA-mediated signalling networks. miRNAs contribute to the regulation of osteoblast and osteoclast activity, as well as macrophage-mediated immune responses, thereby influencing bone regeneration and integration with implant surfaces. This review summarizes current insights into the role of miRNAs at the bone-implant interface, focusing particularly on their involvement in immune modulation and bone tissue formation. Furthermore, it explores emerging strategies for the local delivery of miRNAs to enhance implant integration, highlighting their therapeutic potential in improving orthopaedic outcomes.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"864-879"},"PeriodicalIF":5.5,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13368402/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148444244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparisons of phantom-based and phantomless QCT bone mineral density for predicting subsequent fractures.","authors":"Jian Geng, Zitong Cheng, Yandong Liu, Dongfeng Xu, Wenshuang Zhang, Yi Yuan, Bo Hu, Jing Zheng, Ling Wang, Chunhua Mai, Xiaoguang Cheng","doi":"10.1302/2046-3758.157.BJR-2025-0580.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2025-0580.R1","url":null,"abstract":"<p><strong>Aims: </strong>This study aimed to compare the agreement between phantom-based (PB-QCT) and phantomless (PL-QCT) quantitative CT bone mineral density (BMD) measurements, and their predictive utility for subsequent fractures in postmenopausal women following percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs).</p><p><strong>Methods: </strong>In this prospective cohort study, 185 OVCF patients underwent lumbar CT with synchronous phantom calibration. BMD was measured via PB-QCT, PL-QCT (using subcutaneous adipose tissue (SAT), psoas muscle, or dual-tissue calibration), and vertebral Hounsfield units (vHU). Agreement was assessed via Bland-Altman analysis, and fracture prediction via Cox regression.</p><p><strong>Results: </strong>Dual-tissue PL-QCT showed the highest agreement with PB-QCT (absolute bias: 0.04 to 2.18 mg/cm³). However, PB-QCT demonstrated superior predictive power: per 1-SD decrease, it predicted 20% to 22% increased risk of spinal fractures (adjusted HR = 1.21, p = 0.032) and any-site fractures (HR = 1.20, p = 0.043), maintaining significance after multivariable adjustment.</p><p><strong>Conclusion: </strong>Despite high agreement - especially between PB-QCT and dual-tissue PL-QCT - PB-QCT demonstrated modest but consistent advantages in predicting subsequent fractures over PL-QCT and vHU. These results reinforce the essential role of standardized phantom calibration for accurate fracture risk stratification in post-PKP patients, while also supporting the potential use of PL-QCT and vHU as opportunistic screening tools in settings where phantom calibration is not feasible.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"850-863"},"PeriodicalIF":5.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148434904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exercise-primed Trpv4+ progenitors sense mechanical to regulate graded transition in enthesis regeneration.","authors":"Shibo Xu, Yiyi Lin, Yihang Yu, Zhiquan Zhu, Pan Huang, Qizhong Xie, Yujianan Chen, Xu Tao, Mei Zhou, Zunhan Liu, Xuting Bian, Lin Guo","doi":"10.1302/2046-3758.157.BJR-2026-0059.R1","DOIUrl":"10.1302/2046-3758.157.BJR-2026-0059.R1","url":null,"abstract":"<p><strong>Aims: </strong>To identify the molecular mechanisms of mechanotransduction that drive functional regeneration rather than scar formation at the tendon-bone interface, addressing the high clinical failure rates of enthesis injuries.</p><p><strong>Methods: </strong>Single-cell RNA sequencing was performed on enthesis tissues at multiple post-injury timepoints. A mouse tendon-bone insertion injury model was established with treadmill exercise versus sedentary controls. Transient receptor potential vanilloid 4 (TRPV4)+ cells were isolated by fluorescence-activated cell sorting for functional assays. Mechanistic studies included bulk RNA sequencing, immunofluorescence, and in vitro mechanical stimulation. Functional outcomes were assessed by histomorphometry, micro-CT, and biomechanical testing.</p><p><strong>Results: </strong>Single-cell transcriptomics identified <i>Trpv4</i>⁺ cells specifically enriched in chondrogenic lineages during enthesis repair. Mechanical stimulation significantly increased <i>Trpv4⁺</i> chondrocyte density and enhanced chondrogenic marker expression. Lineage tracing confirmed that <i>Trpv4</i>⁺ progenitors possess clonogenicity and multipotent differentiation capacity, with mechanical stimulation enhancing their chondrogenic potential. Mechanistically, <i>Trpv4</i> activation facilitated calcium influx, leading to calcineurin-NFATc1 signalling cascade activation. Transplantation of exercise-primed <i>Trpv4</i>⁺ progenitor cells significantly improved cartilage matrix deposition and biomechanical properties compared to controls.</p><p><strong>Conclusion: </strong><i>Trpv4</i> ⁺ progenitors constitute a mechanosensitive population critical for enthesis regeneration. Exercise enhances <i>Trpv4</i>-dependent chondrogenic differentiation through the calcium-calcineurin-NFATc1 axis, providing a scientific basis for optimizing postoperative rehabilitation.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"15 7","pages":"836-849"},"PeriodicalIF":5.5,"publicationDate":"2026-07-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13356974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148429671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}