Connective Tissue Research最新文献

{"title":"Mitochondrial crosstalk between bone marrow stromal cells and chondrocytes: implication for cartilage repair in osteoarthritis.","authors":"Baihui Zhang, Jiasi Zhang, Danyang Yue, Xiao Huang, Jun Pan","doi":"10.1080/03008207.2025.2590044","DOIUrl":"10.1080/03008207.2025.2590044","url":null,"abstract":"<p><strong>Purpose/aim: </strong>Mitochondria are vital dynamic organelles released by cells into extracellular space, endocytosed in or transferred between cells in contact. Mitochondria from healthy bone marrow stem cells (MSCs) show rescue effects on chondrocytes, accordingly a concept of using healthy MSC mitochondria for cartilage regeneration is put forward. Therefore, whether mitochondria from healthy MSCs help to save chondrocytes in damaged cartilage microenvironment is intriguing. We answered this question by considering coexistent MSCs and chondrocytes, and their released mitochondria in damaged joint.</p><p><strong>Materials and methods: </strong>Mitochondria were extracted from primarily cultured MSCs and chondrocytes of osteoarthritis (OA) human patients to represent mitochondria released endogenously by MSCs and chondrocytes in damaged joint. While mitochondria were extracted from healthy rats to represent mitochondria exogenously added during MSC mitochondrial repair for the inaccessibility of healthy human. The mitochondria were co-cultured with another type of cells. Endocytosing and afterward positioning of exogenous mitochondria, as well as induced alterations in mitochondria and cellular behaviors of recipient cells were assayed.</p><p><strong>Result: </strong>Our results suggested that although mitochondria from healthy MSCs advantaged remedy for inflammatory chondrocytes, mitochondria from healthy and OA chondrocytes, as well as from OA MSCs disadvantaged chondrocytes remedy, no matter the mitochondria were from the same or different species. However, reactive oxygen species (ROS) modulation alleviated the disadvantage.</p><p><strong>Conclusions: </strong>Our results provide a reminder for careful consideration of mitochondrial therapy, and explanation for unsuccessful repair of damaged cartilage by MSCs from aspect of mitochondria, as well as potential remedy through ROS modulation.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"140-156"},"PeriodicalIF":2.1,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145596105","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":"Notum disrupts Wnt/β-catenin-mediated BMP9 osteogenesis in MSCs: implications for bone regeneration.","authors":"Wen-Ge He, Xin-Yue Wan, Yin-Kun Hu, Yu-Mei Wang, Zheng-Hao Xu, Zhong Gan, Liang Chen","doi":"10.1080/03008207.2025.2582827","DOIUrl":"10.1080/03008207.2025.2582827","url":null,"abstract":"<p><strong>Purpose: </strong>Bone morphogenetic protein 9 (BMP9) is a cytokine with potent osteoinductive activity, although its precise regulatory mechanisms remain incompletely elucidated. NOTUM, a secreted palmitoleoyl-protein carboxylesterase, has an unclear role in osteogenic differentiation. This study aims to explore the role and mechanism of NOTUM in BMP9-induced osteogenic differentiation of mouse embryonic fibroblasts (MEFs).</p><p><strong>Methods to methods: </strong>In the BMP9-induced osteogenic differentiation model, Notum was either overexpressed or silenced, and the expression of RUNX2 and OPN as well as osteogenic signaling pathways were assessed by q-PCR and Western blot. ALP staining and Alizarin Red staining were subsequently performed to determine ALP activity and matrix mineralization. Furthermore, the osteogenic effect of Notum was evaluated using an in vivo subcutaneous ectopic osteogenesis model, supplemented by histochemical staining and micro-CT analysis.</p><p><strong>Results: </strong>BMP9 significantly downregulates NOTUM protein expression in MEF cells. NOTUM attenuated BMP9-induced expression of osteogenic markers RUNX2 and OPN, as well as ALP activity and matrix mineralization. In vivo ectopic osteogenesis assays yielded results consistent with in vitro observations. Mechanistically, NOTUM overexpression reduced β-catenin protein levels, while NOTUM knockdown elevated β-catenin accumulation during BMP9-mediated osteogenic differentiation. NOTUM overexpression up-regulated GSK-3β protein expression while suppressing its phosphorylation status during BMP9-induced osteogenesis, whereas NOTUM depletion produced the converse effects. Pharmacological activation of the Wnt/β-catenin signaling pathway rescued osteogenic marker expression, effectively counteracting NOTUM-mediated suppression of BMP9's osteogenic potential.</p><p><strong>Conclusions: </strong>NOTUM serves as a novel regulator of BMP9-Induced osteogenesis via modulation of the Wnt/β-Catenin Axis, Suggesting its potential as a therapeutic target for bone regeneration.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"84-98"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511893","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":"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":"10.1080/03008207.2025.2565592","url":null,"abstract":"<p><strong>Purpose: </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":"51-68"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","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":"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":"10.1080/03008207.2025.2554842","url":null,"abstract":"<p><strong>Purpose: </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>Conclusions: </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":"27-37"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","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":"Connections give strength: building next layer of Connective Tissue Research.","authors":"Muhammad Farooq Rai","doi":"10.1080/03008207.2026.2593688","DOIUrl":"10.1080/03008207.2026.2593688","url":null,"abstract":"","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":"67 1","pages":"1"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145803340","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":"Protective effects of Apelin-13 on steroid-induced osteonecrosis of the femoral head in rats.","authors":"Ozancan Biçer, Ozan Beytemur, Mustafa Fatih Daşci, Muhammed Uslu, Yiğit Güleryüz, Yiğit Önaloğlu, Emin Can Balci, Büşra Yaprak Bayrak","doi":"10.1080/03008207.2025.2573679","DOIUrl":"10.1080/03008207.2025.2573679","url":null,"abstract":"<p><strong>Purpose: </strong>Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by bone tissue necrosis due to vascular insufficiency, often triggered by corticosteroid use. Steroids are commonly employed in the management of autoimmune diseases, organ transplantation, and COVID-19. Early detection is crucial, as ONFH primarily affects young and middle-aged individuals and often progresses to femoral head collapse if untreated. The objective is to evaluate the protective effects of Apelin-13 (Ap-13) on steroid-induced ONFH (SONFH) in a rat model.</p><p><strong>Methods: </strong>Thirty-two female Sprague-Dawley rats were randomized into four groups: Control, Ap-13 only, ONFH, and ONFH + Ap-13. SONFH was induced using lipopolysaccharide (LPS) and methylprednisolone (MPS). The treatment group received daily intraperitoneal Ap-13 injections. At the fourth week, radiological, histopathological, immunohistochemical, and biochemical analyses were conducted on femoral heads.</p><p><strong>Results: </strong>Micro-CT showed no significant differences in bone mineral density or trabecular parameters. Histopathology revealed increased osteonecrosis, empty lacunae, and vascular thrombosis in the ONFH group, which were significantly reduced in the ONFH + Ap-13 group (<i>p</i> < 0.05). Ap-13 decreased serum malondialdehyde (MDA) levels (<i>p</i> = 0.0002), reduced caspase-3 expression (<i>p</i> < 0.05), and elevated VEGF expression (<i>p</i> = 0.046), indicating reduced oxidative stress, apoptosis, and enhanced vascularization. Additionally, LDL and triglyceride levels were significantly lower in the Ap-13 treated group (<i>p</i> < 0.05).</p><p><strong>Conclusions: </strong>Apelin-13 demonstrates protective effects against SONFH by reducing oxidative stress, apoptosis, and improving vascularization. It may represent a promising noninvasive therapeutic strategy for early-stage ONFH.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"69-83"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145444312","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":"Research on E3 ubiquitin ligase TRIM22 knockdown regulating macrophage polarization and osteoclast differentiation through the NF-κB/MAPK pathway.","authors":"Wen Liang, Chao Tang, Yue Wu","doi":"10.1080/03008207.2025.2582833","DOIUrl":"10.1080/03008207.2025.2582833","url":null,"abstract":"<p><strong>Purpose: </strong>The balance of the activities of osteoclasts (OCs) and osteoblasts is essential for maintenance of bone homeostasis. Macrophages polarizing into a pro-inflammatory M1 type are responsible for differentiation of OCs. This project aims to explore the role of tripartite motif containing 22 (TRIM22), a member of the TRIM proteins with pivotal roles in bone immune response, in macrophage polarization and OC differentiation.</p><p><strong>Methods: </strong>Bone marrow macrophages (BMMs) were isolated from femurs and tibias of C57BL/6 mice and stimulated with macrophage colony-stimulating factor (M-CSF) and RANKL to form OCs. LPS and IL-4 were used to induce polarization of BMMs into M1 and M2 macrophages, respectively. RT-qPCR and Western blot assays were conducted to examine the expression of TRIM22 during OC differentiation. The functions of TRIM22 on M1 macrophage polarization and OC differentiation were assessed utilizing loss-of-function experiments <i>in vitro</i>.</p><p><strong>Results: </strong>Increased expression of TRIM22 was found during OC differentiation, while its knockdown in BMMs alleviated OC formation. M1 polarization of BMMs facilitated OC differentiation as opposed to the M2 phenotype that exhibited anti-OC differentiation characteristics. TRIM22 deficiency attenuated M1 macrophage polarization and inflammatory cytokine secretion, concomitant with suppressed OC differentiation. The NF-κB/MAPK pathway inactivation was responsible for this effect of TRIM22 knockdown.</p><p><strong>Conclusions: </strong>These results reveal a critical mechanism for OC differentiation which is mediated by the TRIM22/NF-κB/MAPK signaling, highlighting a possible avenue for further exploration of target molecules in bone diseases.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"99-111"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145457867","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":"Latent TGF-β content of articular cartilage with development and age.","authors":"Sedat Dogru, Nicholas Simone, Halide Z Haciguzeller, Gabriela M Alba, Matthew D Layne, Michael B Albro","doi":"10.1080/03008207.2025.2543383","DOIUrl":"10.1080/03008207.2025.2543383","url":null,"abstract":"<p><strong>Purpose: </strong>An important regulatory feature of transforming growth factor-β (TGF-β) in cartilage stems from its extracellular matrix (ECM) sequestration as an inactive latent complex (LTGF-β), a configuration that enables need-based activation in response to physiologic stimuli. Recent work has elucidated the dysregulation of TGF-β signaling with development, age, and pathology. However, characterizations of LTGF-β content levels in cartilage are limited. Here, we characterize the variation of LTGF-β in articular cartilage with tissue development and age.</p><p><strong>Methods: </strong>LTGF-β evolution with development is characterized via measures of bovine cartilage explants from fetal, skeletally immature (2-4 months), and skeletally mature (60 months) animals. LTGF-β evolution with cartilage aging is characterized via measures of human cartilage explants procured via cadavers (n=19 donors) ranging in age from 13 to 80 years.</p><p><strong>Results: </strong>For bovine cartilage, while LTGF-β per unit tissue volume decreases with development (50.5 ± 22.0 to 16.4 ± 7.4 ng/mL for LTGF-β1; p<0.01; 29.8 ± 10.7 to 12.6 ± 4.1 ng/mL for LTGF- β2; p<0.01), LTGF-β1 and LTGF-β2 contents per cell number in the tissue does not change with development (p>0.41), indicating that the amount of LTGF-β available for each chondrocyte remains conserved. LTGF-β1 content in human tissues exhibits a dynamic range of an order of magnitude (6.4 ± 3.6 to 70.6 ± 21.8 ng/mL), but donor age is not predictive of LTGF-β1 content in cartilage (p=0.87).</p><p><strong>Conclusions: </strong>These results suggest that development and aging are not limiting factors for LTGF-β availability in cartilage.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"2-12"},"PeriodicalIF":1.9,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13126578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144816024","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interleukin-4-loaded calcium alginate composite granules for hemostasis and alveolar bone regeneration after tooth extraction.","authors":"Zhengwen Luo, Kuang-Wen Li, Chengcheng Yu, Tianjiao Yang, Huajun Lin, Luyuan Chen, Zhihui Chen, Tingting Zhao, Yonglong Hong, Wen Sui","doi":"10.1080/03008207.2025.2587065","DOIUrl":"10.1080/03008207.2025.2587065","url":null,"abstract":"<p><strong>Purpose/aim: </strong>Tooth extraction often leads to postoperative bleeding and alveolar bone loss, complicating the healing process. This study aimed to develop interleukin-4 (IL-4)-loaded calcium alginate composite granules (CA@IL-4) as a dual-functional biomaterial to synergistically address these challenges by promoting both hemostasis and bone regeneration.</p><p><strong>Methods: </strong>The CA@IL-4 composite granules were successfully synthesized and characterized. Their biocompatibility and structural stability were evaluated in vitro. The efficacy of the granules was further investigated in a rat tooth extraction model, where hemostatic performance (bleeding time and blood loss) and regenerative capacity were assessed.</p><p><strong>Results: </strong>The synthesized CA@IL-4 material exhibited excellent biocompatibility and stability. In the animal model, CA@IL-4 granules achieved rapid hemostasis, significantly reducing both bleeding time and blood loss compared to the control. Micro-computed tomography and histological analyses after 28 days of healing confirmed that the CA@IL-4 group markedly enhanced alveolar bone regeneration, demonstrating superior bone mineral density (BMD), bone volume fraction (BV/TV), and trabecular architecture compared to the CA-only and untreated groups.</p><p><strong>Conclusions: </strong>The CA@IL-4 composite granule is a promising dual-functional biomaterial that effectively promotes hemostasis and enhances bone regeneration, offering a potent strategy for optimal post-extraction socket management.</p>","PeriodicalId":10661,"journal":{"name":"Connective Tissue Research","volume":" ","pages":"112-124"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145548693","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":"10.1080/03008207.2025.2561655","url":null,"abstract":"<p><strong>Purpose: </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>Conclusions: </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":"38-50"},"PeriodicalIF":2.1,"publicationDate":"2026-01-01","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}