FBS Colloquia No.426Laboratory of Immunology and Cell Biology

TNFα-driven proliferation of osteoclast precursors in situ causes aberrant bone destruction in arthritic joints

Rheumatoid arthritis is an autoimmune disease in which dysregulated immunity drives chronic synovial inflammation and progressive bone destruction. Bone erosion in arthritis is not simply a disorder of skeletal homeostasis, but represents a focal conversion of immune inflammation into tissue destruction. This destructive process is mediated by osteoclasts, multinucleated myeloid-lineage cells specialized for bone resorption. Although osteoclasts are indispensable for physiological bone remodeling, they are aberrantly induced and activated on bone surfaces adjacent to inflamed synovium, leading to erosive structural damage. Our lab has previously identified a population of inflammatory synovial cells with high osteoclastogenic capacity that emerges during arthritis (Hasegawa T. et al., Nat Immunol 2019). In this colloquium, I will present our recent findings on how pathological osteoclast differentiation is induced in arthritic joints and how interactions with neighboring inflammatory cells support the formation of bone-resorbing osteoclasts.