Department of Neurosurgery, Stanford School of Medicine, Stanford University, Palo Alto, CA 94304, USA.
Department of Anatomy, Faculty of Veterinary Sciences, Campus de Vegazana, University of Léon-Universidad de León, 24071 León, Spain.
Int J Mol Sci. 2024 Oct 20;25(20):11287. doi: 10.3390/ijms252011287.
Osteoarthritis (OA) is a degenerative joint disease characterized by cartilage degradation and inflammation. This study investigates the therapeutic potential of secretome derived from adipose tissue mesenchymal stem cells (ASCs) in mitigating inflammation and promoting cartilage repair in an in vitro model of OA. Our in vitro model comprised chondrocytes inflamed with TNF. To assess the therapeutic potential of secretome, inflamed chondrocytes were treated with it and concentrations of pro-inflammatory cytokines, metalloproteinases (MMPs) and extracellular matrix markers were measured. In addition, secretome-treated chondrocytes were subject to a microarray analysis to determine which genes were upregulated and which were downregulated. Treating TNF-inflamed chondrocytes with secretome in vitro inhibits the - pathway, thereby mediating anti-inflammatory and anti-catabolic effects. Additional protective effects of secretome on cartilage are revealed in the inhibition of hypertrophy markers such as RUNX2 and COL10A1, increased production of COL2A1 and ACAN and upregulation of . These findings suggest that ASC-derived secretome can effectively reduce inflammation, promote cartilage repair, and maintain chondrocyte phenotype. This study highlights the potential of ASC-derived secretome as a novel, non-cell-based therapeutic approach for OA, offering a promising alternative to current treatments by targeting inflammation and cartilage repair mechanisms.
骨关节炎（OA）是一种退行性关节疾病，其特征为软骨降解和炎症。本研究旨在探讨脂肪组织间充质干细胞（ASCs）来源的外泌体在体外 OA 模型中减轻炎症和促进软骨修复的治疗潜力。我们的体外模型由 TNF 诱导的软骨细胞组成。为了评估外泌体的治疗潜力，用其处理炎性软骨细胞，并测量促炎细胞因子、金属蛋白酶（MMPs）和细胞外基质标志物的浓度。此外，对经外泌体处理的软骨细胞进行微阵列分析，以确定上调和下调的基因。外泌体在体外处理 TNF 诱导的软骨细胞可抑制 NF-κB 通路，从而发挥抗炎和抗分解代谢作用。外泌体对软骨的额外保护作用还表现在抑制肥大标志物如 RUNX2 和 COL10A1，增加 COL2A1 和 ACAN 的产生以及上调 SOX9。这些发现表明 ASC 来源的外泌体可有效减轻炎症、促进软骨修复并维持软骨细胞表型。本研究强调了 ASC 来源的外泌体作为一种新型非细胞治疗 OA 的方法的潜力，通过靶向炎症和软骨修复机制为当前治疗提供了有前景的替代方案。
