Aging
Navigate
Submit an Article
Research Paper|Volume 16, Issue 11|pp 9558—9568

The protective effects of orexin-A in alleviating cell senescence against interleukin-1β (IL-1β) in chondrocytes

Lin Shen1, Xiantie Zeng1, Haiying Zhang2
  • 1Department of Orthopedics, Tianjin Hospital, Tianjin 300211, China
  • 2Department of Orthopedics, Dongfang Hospital, Beijing University of Traditional Chinese Medicine, Beijing 100078, China
Received: September 22, 2023Accepted: March 3, 2024Published: May 31, 2024
https://doi.org/10.18632/aging.205884

Copyright: © 2024 Shen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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.