TNFSF11 and rheumatoid arthritis: Classically, in the presence of macrophage colony-stimulating factor (M-CSF), the receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL) pathway and costimulatory signaling pathways synergistically trigger osteoclastogenesis.36,37 In the pathogenesis of RA, osteoclasts colonize the interface between the inflamed synovium and the periarticular bone surface.