Open AccessGα12 regulates osteoclastogenesis by modulating NFAT c1 expression
Author(s) -
Song MinKyoung,
Park Cheolkyu,
Lee Yong Deok,
Kim Haemin,
Kim Min Kyung,
Kwon JunOh,
Koo Ja Hyun,
Joo Min Sung,
Kim Sang Geon,
Kim HongHee
Publication year - 2018
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.13370
Subject(s) - rhoa , rankl , nfat , osteoclast , bone resorption , activator (genetics) , microbiology and biotechnology , knockout mouse , chemistry , transcription factor , resorption , cellular differentiation , signal transduction , receptor , endocrinology , biology , biochemistry , gene
Abstract The G12 family of G protein alpha subunits has been shown to participate in the regulation of various physiological processes. However, the role of Gα12 in bone physiology has not been well described. Here, by micro‐ CT analysis, we discovered that Gα12‐knockout mice have an osteopetrotic phenotype. Histological examination showed lower osteoclast number in femoral tissue of Gα12‐knockout mice compared to wild‐type mice. Additionally, in vitro osteoclastic differentiation of precursor cells with receptor activator of nuclear factor‐κB ligand ( RANKL ) showed that Gα12 deficiency decreased the number of osteoclast generated and the bone resorption activity. The induction of nuclear factor of activated T‐cell c1 ( NFAT c1), the key transcription factor of osteoclastogenesis, and the activation of RhoA by RANKL was also significantly suppressed by Gα12 deficiency. We further found that the RANKL induction of NFAT c1 was not dependent on RhoA signalling, while osteoclast precursor migration and bone resorption required RhoA in the Gα12‐mediated regulation of osteoclasts. Therefore, Gα12 plays a role in differentiation through NFAT c1 and in cell migration and resorption activity through RhoA during osteoclastogenesis.