Relaxin-2 Counteracts TNF-α-Induced Senescence in Human Primary Chondrocytes by Enhancing Telomerase Activity and Modulating SIRT1/p53 Signaling.

Abstract

The pro-inflammatory cytokine TNF-α plays a crucial role in promoting cellular senescence in chondrocytes, contributing to the pathological progression of osteoarthritis (OA). Relaxin-2, a biologically active peptide hormone with diverse effects, has been investigated for its potential protective role against TNF-α-induced cellular senescence in human primary chondrocytes. In this study, human primary chondrocytes were exposed to TNF-α (10ng/mL) with and without the presence of recombinant human relaxin-2 (rh relaxin-2). SA-β-gal staining indicated that rh relaxin-2 effectively mitigated TNF-α-induced cellular senescence in these cells. Furthermore, rh relaxin-2 enhanced telomerase activity and prevented cell cycle arrest at the G0/G1 phase induced by TNF-α. Additionally, rh relaxin-2 reduced the expression levels of plasminogen activator Inhibitor-1 (PAI-1) and p21, key regulators of cellular senescence. Interestingly, TNF-α increased K382 acetylation of p53 but decreased SIRT1 expression. Notably, knocking down SIRT1 negated the protective effects of rh relaxin-2 on cellular senescence, suggesting that SIRT1 is involved in mediating the protective effects of rh relaxin-2. These findings provide new insights into the potential therapeutic use of rh relaxin-2 for OA treatment through a novel mechanism.