The Death Receptor 3–TNF-like protein 1A pathway drives adverse bone pathology in inflammatory arthritis

摘要: Rheumatoid arthritis (RA) is a chronic inflammatory disease of synovial joints that associated with cartilage and bone destruction. Death Receptor 3 (DR3), tumor necrosis factor (TNF) receptor superfamily member, has recently been the pathogenesis RA. We demonstrate absence DR3 confers resistance to development adverse pathology in experimental antigen-induced (AIA). DR3ko mice exhibited reduction all histopathological hallmarks AIA but, particular, failed develop subchondral erosions were completely protected from this characteristic AIA. In contrast, TNF-like protein 1A (TL1A), ligand for DR3, exacerbated dose- DR3-dependent fashion. Analysis osteoclast number within joint revealed areas susceptible erosion mice, whereas vitro osteoclastogenesis assays showed TL1A could directly promote mouse man. Treatment antagonistic anti-TL1A mAb animals systemic model RA collagen-induced arthritis. therefore conclude DR3–TL1A pathway regulates destruction two murine models represents potential novel target therapeutic intervention disease.