Macrophages: pivotal orchestrators and emerging therapeutic targets in osteoarthritis pathogenesis

Osteoarthritis (OA) is a heterogeneous total joint disease that can cause disability, affecting over 500 million people worldwide. Macrophages play an important regulatory role in OA progression through orchestrating synovial inflammation and degradation of the cartilage matrix. The polarization and inflammatory functions of macrophages are coordinately regulated by multiple signaling pathways, including PI3K/Akt, NF-κB, mTORC1, Wnt/β-catenin, and MAPK. At present, the pathogenesis of OA is not fully understood, and effective treatment methods are lacking. Therefore, clarifying the regulatory mechanism and therapeutic potential of macrophages in OA provides direction for the development of more effective pharmacological interventions. In this review, we summarize the epidemiology and pathogenesis of OA, highlights the role of macrophages in the development of OA and related molecular targets, and discusses the latest drug research progress in targeting macrophage-mediated pathways in OA.