PDF(Pubmed)
Abstract：
Osteoarthritis (OA) is one of the most important causes of global disability, and dysfunction of chondrocytes is an important risk factor. The treatment of OA is still a challenge. Orexin-A is a hypothalamic peptide, and its effects in OA are unknown. In this study, we found that exposure to interleukin-1β (IL-1β) reduced the expression of orexin-2R, the receptor of orexin-A in TC-28a2 chondrocytes. Importantly, the senescence-associated β-galactosidase (SA-β-gal) staining assay demonstrated that orexin-A treatment ameliorates IL-1β-induced cellular senescence. Importantly, the presence of IL-1β significantly reduced the telomerase activity of TC-28a2 chondrocytes, which was rescued by orexin-A. We also found that orexin-A prevented IL-1β-induced increase in the levels of Acetyl-p53 and the expression of p21. It is shown that orexin-A mitigates IL-1β-induced reduction of sirtuin 3 (SIRT3). Silencing of SIRT3 abolished the protective effects of orexin-A against IL-1β-induced cellular senescence. These results imply that orexin-A might serve as a promising therapeutic agent for OA.
摘要：
骨关节炎(OA)是导致全球残疾的重要原因之一。软骨细胞功能障碍是一个重要的危险因素。OA的治疗仍然是一个挑战。Orexin-A是一种下丘脑肽,其对OA的影响尚不清楚。在这项研究中,我们发现暴露于白细胞介素-1β（IL-1β）降低了食欲素-2R的表达，TC-28a2软骨细胞食欲素A受体。重要的是,衰老相关的β-半乳糖苷酶（SA-β-gal）染色实验表明，食欲素A治疗可改善IL-1β诱导的细胞衰老。重要的是,IL-1β的存在显著降低了TC-28a2软骨细胞的端粒酶活性,由orexin-A救出。我们还发现食欲素A可防止IL-1β诱导的乙酰p53水平和p21表达的增加。显示食欲素A减轻IL-1β诱导的沉默调节蛋白3（SIRT3）的减少。SIRT3的沉默消除了食欲素A对IL-1β诱导的细胞衰老的保护作用。这些结果表明食欲素A可能是一种有前途的OA治疗剂。
