Primary cilia and inflammatory response: unveiling new mechanisms in osteoarthritis progression.

Abstract

Osteoarthritis (OA) is a common degenerative joint disease that can lead to chronic pain and disability. The pathogenesis of OA involves chronic low-grade inflammation, characterized by the degradation of chondrocytes, inflammation of the synovium, and systemic low-grade inflammation. This inflammatory response accelerates the progression of OA and contributes to pain and functional impairment. Primary cilia play a crucial role in cellular signal transduction and the maintenance of cartilage matrix homeostasis, and their dysfunction is closely linked to inflammatory responses. Given these roles, primary cilia may significantly contribute to the pathogenesis of OA. This review explores inflammation-associated signaling pathways in OA, including NF-κB, MAPK, JAK/STAT, and PI3K/AKT/mTOR signaling. In addition, we place particular emphasis on cilia-mediated inflammatory modulation in OA. Primary cilia mediate chondrocyte responses to mechanical loading and inflammatory cytokines via pathways including NF-κB, MAPK, TRPV4, and Hedgehog signaling. Notably, alterations in the length and incidence of primary cilia in chondrocytes during OA further underscore their potential role in disease pathogenesis. The identification of biomarkers and therapeutic targets related to primary cilia and inflammatory pathways offers new potential for the treatment and management of OA.