Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong University, Nantong, Jiangsu, 226001, China; Medical College, Nantong University, Nantong, Jiangsu, 226001, China.
Department of Orthopaedics, The Sixth People's Hospital of Nantong, Nantong, Jiangsu, 226001, China.
Tissue Cell. 2022 Jun;76:101765. doi: 10.1016/j.tice.2022.101765. Epub 2022 Feb 22.
Cartilage stem/progenitor cells (CSPCs) was recently isolated and identified from the cartilage tissue. CSPCs is essential for repair and regeneration of cartilage in osteoarthritis (OA). Aging is a primary risk factor for cartilage damage and joint OA. Although studies have confirmed the link between cell aging and OA, the underlying molecular mechanisms regulating CSPCs aging are not fully understood. In this study, we investigated the role of Pin1 in the aging of rat knee joint CSPCs. We isolated CSPCs from rat knee joints and demonstrated that, in long-term in vitro culture, Pin1 protein levels are significantly reduced. At the same time, expression of the senescence-related β-galactosidase and the senescence marker p16 were markedly elevated. In addition, Pin1 overexpression reversed the progression of cellular senescence, as evidenced by the down-regulation of senescence-related β-galactosidase, increased EdU positive cells and diminished levels of p16. In contrast, Pin1 siRNA incorporation promoted CSPCs senescence. In addition, we also observed the distribution of cell cycles through flow cytometry and revealed that Pin1 deficiency results in cell cycle arrest in the G1 phase, suggesting severe lack of proliferation ability, a sign of cellular senescence. Collectively, these results validated that Pin1 is an essential regulator of CSPCs aging.
软骨干细胞/祖细胞（CSPCs）最近从软骨组织中分离和鉴定出来。CSPCs 对于骨关节炎（OA）中软骨的修复和再生至关重要。衰老是软骨损伤和关节 OA 的主要危险因素。尽管研究已经证实了细胞衰老与 OA 之间的联系，但调节 CSPCs 衰老的潜在分子机制尚不完全清楚。在这项研究中，我们研究了 Pin1 在大鼠膝关节 CSPCs 衰老中的作用。我们从大鼠膝关节中分离出 CSPCs，并证明在长期体外培养中，Pin1 蛋白水平显著降低。同时，衰老相关的β-半乳糖苷酶和衰老标志物 p16 的表达明显升高。此外，Pin1 的过表达逆转了细胞衰老的进程，表现为衰老相关的β-半乳糖苷酶的下调、EdU 阳性细胞的增加和 p16 水平的降低。相反，Pin1 siRNA 的掺入促进了 CSPCs 的衰老。此外，我们还通过流式细胞术观察细胞周期的分布，并发现 Pin1 缺乏导致细胞周期停滞在 G1 期，表明增殖能力严重缺乏，这是细胞衰老的一个标志。综上所述，这些结果证实了 Pin1 是 CSPCs 衰老的一个重要调节因子。
