RIPK1 inhibition attenuates experimental autoimmune arthritis via suppression of osteoclastogenesis

• Main Authors: Jooyeon Jhun, Seung Hoon Lee, Se-Young Kim, Jaeyoon Ryu, Ji Ye Kwon, Hyun Sik Na, KyoungAh Jung, Su-Jin Moon, Mi-La Cho, Jun-Ki Min
• Format: Article
• Language: English
• Published: BMC 2019-03-01
• Series: Journal of Translational Medicine
• Subjects: Rheumatoid arthritis; Necrostatin-1s; Osteoclastogenesis; Necroptosis
• Online Access: http://link.springer.com/article/10.1186/s12967-019-1809-3

Abstract Background Rheumatoid arthritis (RA) is a chronic and systemic inflammatory disease characterized by upregulation of inflammatory cell death and osteoclastogenesis. Necrostatin (NST)-1s is a chemical inhibitor of receptor-interacting serine/threonine-protein kinase (RIPK)1, which plays a role in necroptosis. Methods We investigated whether NST-1s decreases inflammatory cell death and inflammatory responses in a mouse model of collagen-induced arthritis (CIA). Results NST-1s decreased the progression of CIA and the synovial expression of proinflammatory cytokines. Moreover, NST-1s treatment decreased the expression of necroptosis mediators such as RIPK1, RIPK3, and mixed lineage kinase domain-like (MLKL). In addition, NST-1s decreased osteoclastogenesis in vitro and in vivo. NST-1s downregulated T helper (Th)1 and Th17 cell expression, but promoted Th2 and regulatory T (Treg) cell expression in CIA mice. Conclusions These results suggest that NST-1s attenuates CIA progression via the inhibition of osteoclastogenesis and might be a potential therapeutic agent for RA therapy.