Connective Tissue Research最新文献

{"title":"Mechanical stimulation of extracellular vesicles secreted by bone marrow mesenchymal stem cells promotes osteoblast proliferation and differentiation by activating the Wnt/β - catenin signaling pathway.","authors":"Hongwei Cui, Yan Wang, Dong Wang, Hui Zhang, Liyuan Zhou, Mengran Qin, Guang Li, Tiancheng Ma, Yanxin Li, Benchao Dong, Peichuan Yang, Zhibin Zhang, Jianxiong Ma, Xinlong Ma","doi":"10.1080/03008207.2025.2565592","DOIUrl":"https://doi.org/10.1080/03008207.2025.2565592","url":null,"abstract":"<p><strong>Introduction: </strong>Osteoporosis is characterized by decreased bone mass, microstructural deterioration of bone tissue, and increased bone fragility. Bone marrow mesenchymal stem cells (BMSCs) are essential for bone growth and repair. Exosomes, which are key mediators of intercellular communication, participate in various biological processes. Although previous studies mainly focused on exosomes from non-stimulated cells during bone remodeling, this study aims to evaluate the therapeutic effects and mechanisms of exosomes derived from mechanically stimulated BMSCs (MS-Exo) compared to conventional exosomes in glucocorticoid-induced osteoporosis (GIOP).</p><p><strong>Methods: </strong>An in vitro GIOP model was created by treating MC3T3-E1 osteoblasts with dexamethasone. A 10% strain was identified as the optimal mechanical stimulation intensity for generating MS-Exo. Cell proliferation was evaluated using CCK-8 and EdU assays, while osteogenic differentiation and mineralization were assessed with ALP and ARS staining. The expression of osteogenic marker genes was measured via qRT-PCR. The mechanisms of MS-Exo were further examined through transcriptomic analysis, immunofluorescence, and qRT-PCR, focusing on the Wnt/β-catenin signaling pathway and its downstream transcription factor TCF7.</p><p><strong>Results: </strong>The findings showed that MS-Exo more effectively reversed dexamethasone-induced suppression of MC3T3-E1 cell proliferation, osteogenic differentiation, and mineralization compared to conventional exosomes. Transcriptomic analysis revealed significant enrichment of the Wnt/β-catenin signaling pathway. Experimental validation confirmed that MS-Exo activated this pathway, increasing the expression of β-catenin, LRP6, and TCF7, while decreasing GSK-3β. The pro-osteogenic effects of MS-Exo were partially reduced by the Wnt pathway inhibitor Dkk-1.</p><p><strong>Conclusion: </strong>Exosomes derived from mechanically stimulated BMSCs promote osteoblast proliferation and differentiation by activating the Wnt/β-catenin signaling pathway and its transcription factor TCF7, providing a promising therapeutic strategy for GIOP.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-18"},"PeriodicalIF":2.1,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dapagliflozin attenuates lipotoxic tenocyte injury via PPARα activation and irisin-driven antioxidant pathways.","authors":"Min Kyung Pyo, Jun Hwi Ko, Do Su Lim, Hyeon Ji Gwon, A M Abd El-Aty, Hacı Ahmet Aydemir, Ji Hoon Jeong, Tae Woo Jung","doi":"10.1080/03008207.2025.2561655","DOIUrl":"https://doi.org/10.1080/03008207.2025.2561655","url":null,"abstract":"<p><strong>Objective: </strong>Dapagliflozin (DAP), an SGLT2 inhibitor commonly prescribed for type 2 diabetes, has been recognized for its anti-inflammatory and antioxidative effects in various disease contexts. However, its impact on hyperlipidemic tenocytes-particularly within the framework of obesity-induced tendinopathy-remains underexplored. This study investigated the protective role of DAP in palmitate-exposed tenocytes, which simulate lipid-induced tendon degeneration.</p><p><strong>Methods: </strong>Protein expression was analyzed via Western blotting, while apoptosis was assessed through cell viability assays, caspase-3 activity, and TUNEL staining. Oxidative stress was evaluated through the quantification of H₂O₂, malondialdehyde (MDA), and reactive oxygen species (ROS). PPARα gene silencing was conducted via siRNA transfection.</p><p><strong>Results: </strong>DAP treatment significantly attenuated apoptosis and oxidative stress, restored the extracellular matrix (ECM) balance, and enhanced tenocyte migration. These protective effects were associated with the upregulation of PPARα, PGC1α, and Nrf2, along with increased activities of antioxidant enzymes such as superoxide dismutase (SOD) and catalase. Notably, silencing PPARα negated the beneficial effects of DAP, underscoring its central role. Furthermore, irisin-a myokine upregulated by DAP in myocytes-was also found to reduce oxidative stress and apoptosis in palmitate-treated tenocytes.</p><p><strong>Conclusion: </strong>This study provides novel insights into the mechanistic actions of DAP in musculoskeletal repair and highlights its potential in mitigating the cellular consequences of metabolic stress. By advancing therapeutic strategies rooted in metabolic regulation and cellular resilience, these findings support the development of safer, more effective interventions for chronic degenerative conditions associated with obesity.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-13"},"PeriodicalIF":2.1,"publicationDate":"2025-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of EMT-related subtype and a 9 genes signature predicts the prognosis in osteosarcoma.","authors":"Feng Zhou, Xuezheng Xu, Yi Luo, Jianfan Liu, Jie Bu","doi":"10.1080/03008207.2025.2554842","DOIUrl":"https://doi.org/10.1080/03008207.2025.2554842","url":null,"abstract":"<p><strong>Objective: </strong>Osteosarcoma, mainly arising from mesenchymal cells, is the most common bone tumor in children and adolescents, with high malignancy and a tendency for metastasis and recurrence. Epithelial cells undergoing epithelial-mesenchymal transition (EMT) often signal the start of tumor metastasis, as they gain mesenchymal characteristics that enhance their migration and invasion capabilities.</p><p><strong>Methods: </strong>Osteosarcoma patient gene expression and clinical data were retrieved from the TARGET database. EMT-related molecular subtypes were identified through consensus clustering. Immune microenvironment assessment was performed using the ESTIMATE algorithm. Using WGCNA, a co-expression network was developed to find modules linked to subtypes. Univariate Cox regression analysis identified prognosis-related genes. The development of a 9-gene prognostic risk model involved Lasso-Cox regression, and its accuracy was verified.</p><p><strong>Results: </strong>Two molecular subtypes (C1 and C2) with distinct clinical outcomes were identified. The C1 group showed significantly higher immune and ESTIMATE scores compared to C2. Through WGCNA, the PINK module was identified as significantly associated with the subtypes. Cox regression analysis revealed 19 prognosis-related genes. A 9-gene risk model (EPHB3, GADD45GIP1, RAD23A, NGDN, SYCE2, SCD, AP1M1, POLR3D, FADS2) was constructed, demonstrating high predictive accuracy. Multivariate Cox analysis indicated GADD45GIP1, NGDN, AP1M1, and POLR3D as independent prognostic factors for osteosarcoma.</p><p><strong>Conclusion: </strong>Two EMT-related subtypes with distinct immune features were identified, aiding clinical decision-making. A model comprising 9 genes offers a dependable means of predicting osteosarcoma prognosis.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"1-11"},"PeriodicalIF":2.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144991662","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Charting the evolving paradigm of osteoarthritis research.","authors":"Muhammad Farooq Rai","doi":"10.1080/03008207.2025.2553418","DOIUrl":"https://doi.org/10.1080/03008207.2025.2553418","url":null,"abstract":"","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"66 5","pages":"311-312"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145148200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of anterior cruciate ligament injury-induced disruption of joint homeostasis and onset of osteoarthritis.","authors":"Robert H Brophy, Richard M Silverman, Muhammad Farooq Rai","doi":"10.1080/03008207.2025.2490097","DOIUrl":"10.1080/03008207.2025.2490097","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a progressive joint disorder that leads to pain and disability for millions of people worldwide. Post-traumatic OA (PTOA), a form of OA, arises secondary to joint injury and often impacts younger individuals. Among the most common joint injuries leading to disrupted joint homeostasis and PTOA is anterior cruciate ligament (ACL) rupture. Even with successful surgical stabilization, the risk of developing PTOA persists due to several factors, including altered biology that contributes to disease progression. Recent research into the biology of ACL injuries has advanced our understanding of the mechanisms by which PTOA develops, including the inflammatory pathways involved, the expression of biomarkers specific to ACL injuries, and their interaction with factors such as the chronicity of the injury. Evidence suggests that homeostatic balance of anabolic and catabolic processes in the knee is disturbed after ACL tears, triggering a catabolic and degenerative phenotype, ultimately leading to premature joint degeneration, pain, and disability. Several key knowledge gaps exist, such as the determinants of the transition from acute to chronic inflammation, inter-patient variability in inflammatory responses, and influence of systemic factors on disease development. PTOA research faces numerous challenges, including protracted nature of the disease, the complexity of joint biology, and difficulties in translating molecular discoveries into clinical practice. Future research should prioritize improving biomarker precision for early detection, developing targeted therapies, and leveraging emerging technologies like machine learning to personalize treatment. This approach will enhance our understanding of the biological basis of PTOA resulting from ACL injuries and identify opportunities to mitigate the long-term consequences of these injuries.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"380-386"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143983957","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Application of knee joint distraction: challenges and opportunities.","authors":"M P Jansen, S C Mastbergen","doi":"10.1080/03008207.2025.2490796","DOIUrl":"10.1080/03008207.2025.2490796","url":null,"abstract":"<p><p>Knee osteoarthritis (OA) is a debilitating condition with limited treatment options beyond symptom management or total knee arthroplasty (TKA). For younger patients, TKA presents challenges, including higher failure rates and revision surgeries. Knee joint distraction (KJD) has emerged as a promising joint-preserving alternative for end-stage knee OA, demonstrating significant improvements in pain, function, and quality of life in clinical trials and clinical practice. Almost 20 years of research has highlighted KJD's capacity to delay or prevent TKA by promoting cartilage and subchondral bone repair through whole-joint remodeling. Recent studies, including a multicenter trial with a purpose-built distraction device, confirm the treatment's efficacy and durability, with benefits lasting up to 10 years. However, long-term outcomes remain limited, and variability in patient response underscores the need for refined predictive tools. Challenges include the high incidence of pin tract infections during treatment and integrating KJD into routine clinical practice, as highlighted by limited trial enrollment in the UK KARDS trial and variability in healthcare system compatibility. Future research should focus on minimizing complications, improving patient selection through advanced imaging and biomarker analyses, and further understanding the mechanisms underlying KJD-induced joint remodeling. Large-scale trials like the ongoing Dutch GODIVA study are poised to provide robust evidence for KJD's broader adoption, implementation, and reimbursement in healthcare systems. With continued advancements, KJD holds the potential to transform the management of knee OA, offering a viable alternative to TKA for younger patients and addressing a critical unmet need in OA care.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"497-503"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971571","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles in cartilage homeostasis, osteoarthritis, and biomarker discovery.","authors":"Emily J Clarke, Alzbeta Chabronova, Mandy J Peffers","doi":"10.1080/03008207.2025.2524064","DOIUrl":"10.1080/03008207.2025.2524064","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a chronic degenerative disease of the joint, involving cartilage degradation, synovial inflammation, and subchondral bone remodeling. Extracellular vesicles (EVs)-membrane-bound particles released by cells and have emerged as key mediators of intercellular communication in joint homeostasis and OA pathogenesis. EVs facilitate crosstalk between chondrocytes, synovial fibroblasts, and mesenchymal stem cells (MSCs), influencing joint health and disease progression. In OA, EV cargo: including proteins, miRNAs, and lipids, undergoes pathological changes that promote inflammation, matrix degradation, senescence, and calcification. Recent studies demonstrate that OA-derived EVs can induce catabolic and pro-inflammatory responses in recipient cells, while EVs from therapeutic sources such as MSCs, exhibit chondroprotective and anti-inflammatory effects in preclinical models. Additionally, EV surface markers and cargo profiles correlate with OA severity and pain, supporting their utility as minimally invasive biomarkers for early diagnosis and patient stratification. Cross-species comparisons suggest that EV signatures may be conserved, highlighting their translational potential in both human and veterinary medicine. However, the field is limited by variability in EV isolation and characterization methods, which hampers reproducibility and clinical application. To advance the clinical translation of EVs, standardized workflows and a deeper mechanistic understanding of EV function in the joint are essential. Identifying disease-specific EV biomarkers could enable earlier OA diagnosis and personalized treatment strategies, while optimizing therapeutic EVs could support regenerative approaches to slow or reverse joint degeneration and improve outcomes for human patients.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"428-434"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biomarkers of aging as it relates osteoarthritis: we can't improve what we can't measure.","authors":"Brian O Diekman, Ming-Feng Hsueh","doi":"10.1080/03008207.2025.2528792","DOIUrl":"10.1080/03008207.2025.2528792","url":null,"abstract":"<p><p>Aging is the largest risk factor for the development of osteoarthritis (OA), a major contributor to increased years lived with disability. This review reflects on how age-related changes relevant to OA have been measured at various length scales. Key discoveries include increased chondrocyte DNA damage with age and the disruption of matrix homeostasis by cellular senescence. Epigenetic clocks have yet to show predictive value for OA, while transcriptomic changes and miRNA profiles are linked to aging and senescence. Protein biomarkers have gained traction in the context of post-traumatic OA and may also be useful in understanding risk profiles for age-related OA. Post-translational modifications provide insights into protein aging and the rate of matrix turnover at different joint sites. Non-enzymatic crosslinks also increase with age and may be responsible for changes to the mechanical properties of joint tissues. Finally, the walking speed declines with age and predicts incident OA. Despite these advances, more research is needed on age-related changes in tissues beyond cartilage. Efforts should be directed toward identifying biomarkers of aging that can integrate large studies on genetic risk factors with the deep phenotyping done in longitudinal cohort OA studies. Early intervention is crucial for treating OA and other age-related diseases, highlighting the importance of validating sensitive and predictive biomarkers that could support new treatment paradigms. Finally, reversing at least some aspects of age-related decline may be critical for improving joint function. Promising approaches include effective delivery of targeted senolytics and the use of partial reprogramming to rejuvenate chondrocytes.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"352-358"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunomodulatory mechanisms of mesenchymal stem cells in joint preservation in osteoarthritis.","authors":"Mohammed Lakrat, Pallavi Bhattaram, Hicham Drissi","doi":"10.1080/03008207.2025.2536148","DOIUrl":"10.1080/03008207.2025.2536148","url":null,"abstract":"<p><p>Osteoarthritis (OA) remains a major challenge for clinicians and researchers, as current treatments predominantly focus on symptomatic relief without completely addressing the underlying pathogenesis. In this regard, intraarticular injections of mesenchymal stem cells (MSCs) are emerging as a promising choice to mitigate pain and functional impairment in knee OA patients. The strong optimism for this therapeutic modality is based on experimental evidence supporting a role for MSCs in modulating inflammation, as well as encouraging clinical trials reporting safety and significant pain mitigation outcomes. However, inconsistencies related to their therapeutic efficacy remain a key concern. Therefore, a comprehensive understanding of the mechanisms by which MSCs exert their anti-inflammatory and joint-preserving effects is critically needed to ensure wider clinical translation. Recent research underscores the significance of MSCs as biomedicines with the potential to modulate the pro-inflammatory pathobiology of the entire OA joint. Their ability to crosstalk with joint resident cells and the infiltrating immune cells to reduce the overall catabolic load on the OA joints is being recognized as a primary mechanism underlying their therapeutic benefits. In this review, we discuss the significance of intraarticular MSC injections in the field of OA clinical research and focus on the immunomodulatory mechanisms underlying the ability of MSCs to modulate inflammation within OA joints by targeting both immune and resident joint cells. We identify current limitations and highlight the need for multidisciplinary clinical and basic science research to establish innovative approaches to further develop MSC-based therapies as efficacious biomedicines to treat OA patients.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"466-472"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144728470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omics-driven insights into the molecular pathways driving osteoarthritis pathogenesis.","authors":"Paco Mattheus Jacobus Welsing, Said El Bouhaddani, Lin Zhu, Nienke C Nijhof, Simon C Mastbergen, Chunyi Wen, Jaume Bacardit, Cristina Ruiz-Romero, Francisco J Blanco, Ali Mobasheri","doi":"10.1080/03008207.2025.2541291","DOIUrl":"10.1080/03008207.2025.2541291","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a multifactorial, mechano-inflammatory joint disorder characterized by cartilage degradation, synovial inflammation, and subchondral bone remodeling. Despite its high prevalence and significant impact on quality of life, no disease-modifying treatments have been approved. In many other disease areas, advanced omics technologies are impacting the development of advanced therapies. In OA, omics technologies such as genomics, transcriptomics, proteomics, and metabolomics have significantly increased our understanding of OA pathogenesis by uncovering molecular pathways driving disease progression. However, we have yet to see any tangible impact on the development of effective disease-modifying therapies. This review focuses on single- and multi-omics studies in OA, emphasizing their role in identifying molecular subtypes (endotypes) and therapeutic subtypes (theratypes). Multi-omics integration has revealed crosstalk between inflammatory, metabolic, and degradative processes, while spatial proteomics is beginning to provide insights into synovial tissue heterogeneity. However, challenges such as data complexity, lack of standardized frameworks, and limited translational validation hinder rapid progress. Future work will need to leverage artificial intelligence, single-cell, and spatial omics within longitudinal cohort studies. By addressing these challenges, omics-driven research holds promise for helping clinicians differentiating patients presenting with OA and psoriatic arthritis (PsA) affecting the hands or knees, developing personalized OA therapies, and achieving true disease modification beyond symptomatic relief.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"323-330"},"PeriodicalIF":2.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145013986","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}