Induction of Krüppel‐like factor 2 reduces K/BxN serum‐induced arthritis

Krüppel‐like factor 2 ( KLF 2) critically regulates activation and function of monocyte, which plays important pathogenic role in progressive joint destruction in rheumatoid arthritis ( RA ). It is yet to be established the molecular basis of KLF 2‐mediated regulation of monocytes in RA pathogenesis. Herein, we show that a class of compound, HDAC inhibitors ( HDAC i) induced KLF 2 expression in monocytes both in vitro and in vivo . KLF 2 level was also elevated in tissues, such as bone marrow, spleen and thymus in mice after infusion of HDAC i. Importantly, HDAC i significantly reduced osteoclastic differentiation of monocytes with the up‐regulation of KLF 2 and concomitant down‐regulation of matrixmetalloproteinases both in the expression level as well as in the protein level. In addition, HDAC i reduced K/BxN serum‐induced arthritic inflammation and joint destruction in mice in a dose‐dependent manner. Finally, co‐immunoprecipitation and overexpression studies confirmed that KLF 2 directly interacts with HDAC 4 molecule in cells. These findings provide mechanistic evidence of KLF 2‐mediated regulation of K/BxN serum‐induced arthritic inflammation.