Osteoarthritis (OA) is a highly prevalent joint disorder that is tightly correlated with age. As the body ages, cell replication and function decline until homeostasis can no longer be maintained. This process involves cellular senescence as well as replicative senescence. Telomere length, cell cycle arrest, expression of p16 and p53, and the release of senescence-associated β-galactosidase (SA-β-Gal) are all markers of cell senescence. In OA joints, chondrocytes undergo cellular senescence prematurely, thereby ceasing to synthesize and maintain cartilage tissue. Upregulation of proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), and oxidative stress induced by overproduction of reactive oxygen species (ROS) are key events in the pathogenesis of OA. In the present study, we investigated the effects of pinitol, a naturally occurring compound, on the effects of TNF-α on chondrocyte senescence and cell cycle arrest. We found that pinitol has a favorable safety profile in terms of cell viability. Pinitol significantly inhibited cellular senescence and cell cycle arrest in the G0/G1 phase induced by TNF-α. We also found that pinitol could inhibit TNF-α-induced increased telomerase activity and expression of p16 and p53. Importantly, we found that the effects of pinitol may be mediated through rescue of Nrf2 signaling, which is recognized as a key protective factor in OA. This finding was verified through a Nrf2 silencing experiment using Nrf2 siRNA. Together, our findings reveal the potential of pinitol as a safe therapeutic option for the prevention of OA-associated chondrocyte senescence and oxidative stress.

中文翻译：

---

松醇抑制 TNF-α 诱导的软骨细胞衰老


骨关节炎（OA）是一种非常普遍的关节疾病，与年龄密切相关。随着身体衰老，细胞复制和功能下降，直到无法维持体内平衡。这个过程涉及细胞衰老和复制衰老。端粒长度、细胞周期停滞、p16 和 p53 的表达以及衰老相关 β-半乳糖苷酶 (SA-β-Gal) 的释放都是细胞衰老的标志。在骨关节炎关节中，软骨细胞过早地发生细胞衰老，从而停止合成和维持软骨组织。肿瘤坏死因子-α (TNF-α) 等促炎细胞因子的上调以及活性氧 (ROS) 过量产生引起的氧化应激是 OA 发病机制中的关键事件。在本研究中，我们研究了松醇（一种天然存在的化合物）对 TNF-α 对软骨细胞衰老和细胞周期停滞的影响。我们发现松醇在细胞活力方面具有良好的安全性。 Pinitol 显着抑制 TNF-α 诱导的细胞衰老和细胞周期停滞在 G0/G1 期。我们还发现松醇可以抑制 TNF-α 诱导的端粒酶活性增加以及 p16 和 p53 表达。重要的是，我们发现松醇的作用可能是通过拯救 Nrf2 信号传导来介导的，Nrf2 信号被认为是 OA 的关键保护因素。这一发现通过使用 Nrf2 siRNA 的 Nrf2 沉默实验得到了验证。总之，我们的研究结果揭示了松醇作为预防 OA 相关软骨细胞衰老和氧化应激的安全治疗选择的潜力。