Hyaluronic acid (HA) exerts a critical role in the lubricating and buffering properties of synovial fluid in joints. The production of HA is regulated by growth factors, hormones, inflammatory cytokines and mechanical load. The reduction of HA contributes to the progression of osteoarthritis. Herein, we found that d-galactose (d-gal) induced the senescence of rabbit synovial membrane cells, accompanied by decreased HA production. The mRNA level of HA synthase 2 (HAS2) was downregulated by d-gal, as analysed by real-time polymerase chain reaction. Melatonin, an endocrine hormone, can regulate the homeostasis of bone and cartilage. We found that melatonin treatment attenuated d-gal-induced cell senescence and decreased the expression of p21, p16 and pp65 proteins. Melatonin could reverse HA production and maintain HAS2 expression. Furthermore, we revealed that Sirt1 signalling was required for melatonin effects. Sirt1 inhibitor could counteract melatonin-mediated HA production and HAS2 expression. Additionally, Sirt1 overexpression directly antagonized d-gal-induced cell aging and HA downregulation. Taken together, our results suggest that melatonin-Sirt1 signal has a protective effect on synovial membrane cells, enhancing HA synthesis and interrupting cell senescence.

中文翻译：

---

褪黑激素通过 Sirt1 信号减轻 d-半乳糖减少的滑膜细胞透明质酸的产生

透明质酸 (HA) 在关节滑液的润滑和缓冲性能中发挥关键作用。HA 的产生受生长因子、激素、炎性细胞因子和机械负荷的调节。HA的减少有助于骨关节炎的进展。在此，我们发现d-半乳糖 ( d -gal) 诱导兔滑膜细胞衰老，伴随着 HA 产生减少。通过实时聚合酶链反应分析，HA 合酶 2 (HAS2) 的 mRNA 水平被d -gal下调。褪黑激素是一种内分泌激素，可以调节骨骼和软骨的稳态。我们发现褪黑激素治疗减弱了d-gal 诱导细胞衰老并降低 p21、p16 和 pp65 蛋白的表达。褪黑激素可以逆转 HA 的产生并维持HAS2 的表达。此外，我们揭示了褪黑激素效应需要 Sirt1 信号传导。Sirt1 抑制剂可以抵消褪黑激素介导的 HA 产生和HAS2表达。此外，Sirt1 过表达直接拮抗d -gal 诱导的细胞衰老和 HA 下调。总之，我们的结果表明，褪黑激素-Sirt1 信号对滑膜细胞具有保护作用，可增强 HA 合成并阻止细胞衰老。