The Role of Thrombospondins in Osteoarthritis: from Molecular Mechanisms to Therapeutic Potential

Osteoarthritis (OA) is a prevalent chronic degenerative joint disorder characterized by cartilage degeneration, joint inflammation, and pain. The pathogenesis of OA still remains unclear. Among the various factors contributing to OA, the role of extracellular matrix (ECM) proteins, particularly thrombospondins (TSPs), has garnered significant attention. TSPs, a family of multifunctional extracellular matrix glycoproteins, are known to participate in numerous physiological and pathological processes, including cell adhesion, migration, differentiation, angiogenesis, and synaptogenesis through cell-cell and cell-matrix interactions. In this review, we provide a summary of the current understanding of TSP proteins in the pathogenesis of OA, including their effects on cartilage homeostasis, synovial inflammation, and subchondral bone remodeling and arthritic pain. We also review the evidence supporting the potential of TSP proteins as diagnostic biomarkers and therapeutic targets, with a focus on recent advances in cartilage regeneration, gene delivery therapy and pain management. Considering the multifaceted roles of TSP proteins in maintaining articular homeostasis, TSP proteins emerge as promising therapeutic targets for OA.