Aging is a major risk factor for degenerative joint diseases, such as osteoarthritis (OA). Previous studies have confirmed the link between senescent mesenchymal stem cells (MSCs) and OA. Cartilage-derived stem/progenitor cells (CSPCs) with MSCs properties have been extracted from a variety of species. We inferred that the senescence of CSPCs may promote the development of osteoarthritis. However, the cellular and molecular mechanisms of CSPCs senescence remains unknown. In this study, we investigated the role of JAK-STAT signaling pathway in a replicative senescence model of CSPCs. We showed that the late CSPCs (> 15th passage) exhibited distinct senescent phenotypes, including increased proportion of β-gal positive senescent cells and F-actin content, as well as cell cycle arrest. In late CSPCs, the activity of JAK-STAT signaling pathway was significantly increased. Activation of JAK-STAT signaling pathway promoted cell senescence in early CSPCs (< 6th passage). Conversely, pharmacological inhibition or genetic knockdown of JAK-STAT signaling pathway attenuated cell senescence in late CSPCs. In conclusion, our results demonstrated the critical role of JAK-STAT signaling pathway in CSPCs senescence.

衰老是退行性关节疾病的主要危险因素，例如骨关节炎 (OA)。以前的研究已经证实了衰老间充质干细胞 (MSCs) 和 OA 之间的联系。具有 MSCs 特性的软骨源性干/祖细胞 (CSPCs) 已从多种物种中提取。我们推断CSPCs的衰老可能促进骨关节炎的发展。然而，CSPCs衰老的细胞和分子机制仍然未知。在这项研究中，我们研究了 JAK-STAT 信号通路在 CSPCs 复制衰老模型中的作用。我们发现晚期 CSPCs（> 15 代）表现出明显的衰老表型，包括增加的 β-gal 阳性衰老细胞比例和 F-肌动蛋白含量，以及细胞周期停滞。在晚期 CSPC 中，JAK-STAT信号通路的活性显着增加。JAK-STAT 信号通路的激活促进了早期 CSPCs 中的细胞衰老（< 6 代）。相反，JAK-STAT信号通路的药理学抑制或基因敲除减弱了晚期CSPC中的细胞衰老。总之，我们的结果证明了 JAK-STAT 信号通路在 CSPCs 衰老中的关键作用。