Osteoclast formation in the joint. Monocytic cells in the synovium serve as osteoclast precursors. Upon exposure to macrophage colony-stimulating factor (MCSF) and Receptor activator of nuclear factor-kappa B ligand (RANKL) synthesized by T cells and synovial fibroblasts, osteoclasts fuse to polykaryons termed preosteoclasts, which then undergo further differentiation into mature osteoclasts, acquiring specific features such as the ruffled membrane. Inflammatory cytokines such as TNF and IL-1, IL-6, and IL-17 increase the expression of RANKL and thus support osteoclastogenesis in the joint. In contrast, regulatory T cells (Tregs) block osteoclast formation via Cytotoxic T-lymphocyte antigen 4 (CTLA4). Figure obtained with permission from .
Desai and Solomon Arthritis Research & Therapy 2010 12:127 doi:10.1186/ar3035