Abstract：
Osteoarthritis (OA) is described as a chronic degenerative disease characterized by the loss of articular cartilage. Senescence is a natural cellular response to stressors. Beneficial in certain conditions, the accumulation of senescent cells has been implicated in the pathophysiology of many diseases associated with aging. Recently, it has been demonstrated that mesenchymal stem/stromal cells isolated from OA patients contain many senescent cells that inhibit cartilage regeneration. However, the link between cellular senescence in MSCs and OA progression is still debated. In this study, we aim to characterize and compare synovial fluid MSCs (sf-MSCs), isolated from OA joints, with healthy sf-MSCs, investigating the senescence hallmarks and how this state could affect cartilage repair. Sf-MSCs were isolated from tibiotarsal joints of healthy and diseased horses with an established diagnosis of OA with an age ranging from 8 to 14 years. Cells were cultured in vitro and characterized for cell proliferation assay, cell cycle analysis, ROS detection assay, ultrastructure analysis, and the expression of senescent markers. To evaluate the influence of senescence on chondrogenic differentiation, OA sf-MSCs were stimulated in vitro for up to 21 days with chondrogenic factors, and the expression of chondrogenic markers was compared with healthy sf-MSCs. Our findings demonstrated the presence of senescent sf-MSCs in OA joints with impaired chondrogenic differentiation abilities, which could have a potential influence on OA progression.
摘要：
骨关节炎(OA)被描述为以关节软骨丧失为特征的慢性退行性疾病。衰老是细胞对应激源的自然反应。在某些情况下是有益的，衰老细胞的积累与许多与衰老相关的疾病的病理生理学有关。最近,已经证明,从OA患者分离的间充质干细胞/基质细胞含有许多抑制软骨再生的衰老细胞.然而,MSCs细胞衰老与OA进展之间的联系仍存在争议。在这项研究中,我们旨在表征和比较滑液MSCs(SF-MSCs)，与OA关节隔离，健康的sf-MSCs，研究衰老标志以及这种状态如何影响软骨修复。Sf-MSC从健康和患病马的胫骨关节中分离,其具有确定的OA诊断,年龄范围为8至14岁。在体外培养细胞并进行细胞增殖测定的特征。细胞周期分析,ROS检测试验，超微结构分析，和衰老标志物的表达。为了评估衰老对软骨分化的影响，用软骨形成因子在体外刺激OAsf-MSCs长达21天，并将软骨形成标志物的表达与健康sf-MSCs进行比较。我们的研究结果表明，在OA关节中存在衰老sf-MSCs，软骨分化能力受损，这可能对OA的进展有潜在的影响。
