Open AccessInduction of Krüppel‐like factor 2 reduces K/BxN serum‐induced arthritis
Author(s) -
Das Manjusri,
Laha Dipranjan,
Kanji Suman,
Joseph Matthew,
Aggarwal Reeva,
Iwenofu Obiajulu H.,
Pompili Vincent J.,
Jain Mukesh K.,
Das Hiranmoy
Publication year - 2019
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.14041
Subject(s) - chemistry , arthritis , monocyte , inflammation , in vivo , cancer research , in vitro , rheumatoid arthritis , microbiology and biotechnology , immunology , medicine , biology , biochemistry , genetics
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.