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Regulatory mechanism of NFATc1 in RANKL‐induced osteoclast activation
Author(s) -
Song Insun,
Kim Jung Ha,
Kim Kabsun,
Jin Hye Mi,
Youn Bang Ung,
Kim Nacksung
Publication year - 2009
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2009.06.047
Subject(s) - rankl , osteoclast , cathepsin k , bone resorption , microbiology and biotechnology , chemistry , cathepsin , gene , biology , biochemistry , receptor , endocrinology , activator (genetics) , enzyme
NFATc1 is a master regulator of RANKL‐induced osteoclast differentiation and herein we investigate the regulatory mechanism of NFATc1 in osteoclast activation. Inactivation of NFATc1 strongly attenuates RANKL‐induced bone resorption and overexpression of a constitutively active form of NFATc1 in osteoclasts induces formation of actin rings and resorption pits on dentin slices. We demonstrate that NFATc1 binds directly to the promoter regions of its target genes and induces expression of various genes, including LTBP3, ClC7, cathepsin K, MMP9, and c‐Src, which are key players in bone resorption. Thus, NFATc1 is essential for RANKL‐induced osteoclast activation via up‐regulation of osteoclast‐activating genes.