Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation.
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.
Song
Insun
I
National Research Laboratory for Regulation of Bone Metabolism and Disease, Medical Research Center for Gene Regulation, Brain Korea 21, Chonnam National University Medical School, 5 Hak-Dong, Dong-Ku, Gwangju 501-746, Republic of Korea.
Kim
Jung Ha
JH
Kim
Kabsun
K
Jin
Hye Mi
HM
Youn
Bang Ung
BU
Kim
Nacksung
N
D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000502:physiology*; D011401:Promoter Regions, Genetic; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism*
D050778:NFATC Transcription Factors; D053245:RANK Ligand