title: Regulatory mechanism of NFATc1 in RANKL-induced osteoclast activation.
abstract: 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.
authors: 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.
authors: Insun
authors: I
authors: Song
authors: Jung Ha
authors: JH
authors: Kim
authors: Kabsun
authors: K
authors: Kim
authors: Hye Mi
authors: HM
authors: Jin
authors: Bang Ung
authors: BU
authors: Youn
authors: Nacksung
authors: N
authors: Kim
mesh_terms: 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*
chemical_list: D050778:NFATC Transcription Factors; D053245:RANK Ligand