Therapeutic targets in aging-related osteoarthritis: A focus on the extracellular matrix homeostasis

Osteoarthritis (OA) represents a globally prevalent degenerative bone diseases and is the primary contributors to pain and disability among middle-aged and elderly people, thereby imposing significant social and economic burdens. When articular cartilage is in the aging environment, epigenetic modifications, DNA damage and mitochondrial dysfunction lead to cell senescence. Chondrocyte senescence has been identified as a pivotal event in this metabolic dysregulation of the extracellular matrix (ECM). It can affect the composition and structure of ECM, and the mechanical and biological signals transmitted by ECM to senescent chondrocytes affect their physiology and pathology. Over the past few decades, the role of ECM in aging-related OA has received increasing attention. In this review, we summarize the changes of cartilage's major ECM (type II collagen and aggrecan) and the interaction between aging and ECM in OA, and explore therapeutic strategies targeting cartilagae ECM, such as noncoding RNAs, small-molecule drugs, and mesenchymal stem cell (MSC)-derived extracellular vesicles for OA. The aim of this study was to elucidate the potential benefits of ECM-based therapies as novel strategies for the management of OA diseases.