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G?12 regulates osteoclastogenesis by modulating NFATc1 expression.


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 G?12 in bone physiology has not been well described. Here, by micro-CT analysis, we discovered that G?12-knockout mice have an osteopetrotic phenotype. Histological examination showed lower osteoclast number in femoral tissue of G?12-knockout mice compared to wild-type mice. Additionally, in vitro osteoclastic differentiation of precursor cells with receptor activator of nuclear factor-?B ligand (RANKL) showed that G?12 deficiency decreased the number of osteoclast generated and the bone resorption activity. The induction of nuclear factor of activated T-cell c1 (NFATc1), the key transcription factor of osteoclastogenesis, and the activation of RhoA by RANKL was also significantly suppressed by G?12 deficiency. We further found that the RANKL induction of NFATc1 was not dependent on RhoA signalling, while osteoclast precursor migration and bone resorption required RhoA in the G?12-mediated regulation of osteoclasts. Therefore, G?12 plays a role in differentiation through NFATc1 and in cell migration and resorption activity through RhoA during osteoclastogenesis.

SUBMITTER: Song MK 

PROVIDER: S-EPMC5783869 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature

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Gα12 regulates osteoclastogenesis by modulating NFATc1 expression.

Song Min-Kyoung MK   Park Cheolkyu C   Lee Yong Deok YD   Kim Haemin H   Kim Min Kyung MK   Kwon Jun-Oh JO   Koo Ja Hyun JH   Joo Min Sung MS   Kim Sang Geon SG   Kim Hong-Hee HH  

Journal of cellular and molecular medicine 20171027 2


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  ...[more]

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