Chondrocyte Senescence in Osteoarthritis: Potential Targets and Pharmacological Interventions.

Authors

Dunyong Tan, Jiawei Guo, Tianyu Wang, Siyao Yang, Jianquan Liu, Daping Wang, Wencui Li

Published in

Cartilage. Pages 19476035251414314. Feb 26, 2026. Epub Feb 26, 2026.

Abstract

PurposeThis review aims to elucidate the mechanisms underlying chondrocyte senescence in osteoarthritis (OA) from 4 core perspectives: extracellular inflammation, mechanical overload and stress, intracellular metabolic and signaling dysregulation, and genetics-related alterations. It further summarizes emerging therapeutic strategies targeting chondrocyte senescence to address the unmet clinical need for disease-modifying OA interventions.FindingsAccumulating evidence indicates that chondrocyte senescence drives OA progression through multiple interconnected mechanisms. These include amplification of inflammation and extracellular matrix degradation via the senescence-associated secretory phenotype (SASP), disruption of anabolic-catabolic homeostasis, dysregulation of mechanotransduction pathways under excessive mechanical load, and reshaping of intracellular metabolism and redox balance. Additional contributing mechanisms involve epigenetic dysregulation, non-coding RNA-mediated gene modulation, and impaired autophagy. Therapeutic approaches under preclinical or clinical investigation encompass senolytic and senomorphic agents, chondroprotective biological materials, genetic or RNA-based interventions, as well as strategies targeting SASP modulation and extracellular microenvironment repair.ConclusionsChondrocyte senescence serves as a central convergent mechanism in OA pathogenesis and a promising target for disease-modifying therapies. Advances in mechanistic understanding and senescence-targeted interventions offer new avenues for translational innovation, though critical challenges related to specificity, safety, and long-term efficacy require further resolution.

PMID:
41747711
Bibliographic data and abstract were imported from PubMed on 15 Sep 2026.

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