Gα12 Regulates Osteoclastogenesis by Modulating NFATc1 Expression

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Oct 28

PMID 29077264

Citations 7

Authors

Min-Kyoung Song

Cheolkyu Park

Yong Deok Lee

Haemin Kim

Min Kyung Kim

Jun-Oh Kwon

Ja Hyun Koo

Min Sung Joo

Sang Geon Kim

Hong-Hee Kim

Affiliations

Soon will be listed here.

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 (NFATc1), 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 NFATc1 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 NFATc1 and in cell migration and resorption activity through RhoA during osteoclastogenesis.

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