The role of macrophage polarization in rheumatoid arthritis and osteoarthritis: Pathogenesis and therapeutic strategies

Rheumatoid arthritis (RA) and osteoarthritis (OA) are common and debilitating joint disorders affecting millions of individuals worldwide. Despite their distinct pathological features, both conditions share a crucial role of macrophages in disease progression. Macrophages exhibit remarkable plasticity, polarizing into pro-inflammatory M1 or anti-inflammatory M2 phenotypes in response to environmental cues. An imbalance in macrophage polarization, particularly a shift towards the M1 phenotype, contributes to chronic inflammation and joint damage in RA and OA. This review explores the complex interplay between macrophages and various cell types, including T cells, B cells, synovial fibroblasts, osteoclasts, chondrocytes, and adipocytes, in the pathogenesis of these diseases. We discuss the current understanding of macrophage polarization in RA and OA, highlighting the molecular mechanisms involved. Furthermore, we provide an overview of potential therapeutic strategies targeting macrophage polarization, such as disease-modifying anti-rheumatic drugs, traditional Chinese medicine, nanomedicines, proteins, chemical compounds, and physical therapies. By elucidating the precise mechanisms governing macrophage polarization and its interactions with other cells in the joint microenvironment, researchers can identify novel therapeutic targets and develop targeted interventions to alleviate disease progression and improve patient outcomes in RA and OA.