KLF15 deficiency accelerates cartilage destruction in inflammatory arthritis

OBJECTIVE: Kruppel-like factor 15 (KLF15) is a transcription factor that promotes anabolic pathways and suppresses catabolic signalling in joint tissues. KLF15 regulates adipocyte differentiation through peroxisome proliferator-activated receptor-γ (PPARγ), which suppresses inflammation via the nuclear factor-κB pathway. This study aimed to clarify the effects of KLF15 in a mouse model of collagen antibody-induced arthritis (CAIA). METHOD: KO and WT mice were evaluated for KLF15, PPARγ, MMP3, and MMP13 mRNA expression by quantitative polymerase chain reaction, and for pIKKα/β by Western blotting. RESULTS: The arthropathy score was significantly higher in the KO group at 4 weeks, while the synovitis score showed no difference. Positive cell ratios for PPARγ were decreased in the KO group, and pIKKα/β, IL-1β, MMP3, and MMP13 were significantly increased. Western blotting showed significantly increased pIKKα/β expression in KO cells compared to WT cells. CONCLUSION: KO mice may cause articular cartilage destruction by decreasing PPARγ expression and increasing inflammatory cytokines and MMPs via IKKα/β. Modulation of KLF15 could be a potential therapeutic strategy for the treatment of arthritis, including rheumatoid arthritis.