Gα12 regulates osteoclastogenesis by modulating NFATc1 expression

• Published in: Journal of cellular and molecular medicine Vol. 22; no. 2; pp. 849 - 860
• Main Authors: Song, Min‐Kyoung, Park, Cheolkyu, Lee, Yong Deok, Kim, Haemin, Kim, Min Kyung, Kwon, Jun‐Oh, Koo, Ja Hyun, Joo, Min Sung, Kim, Sang Geon, Kim, Hong‐Hee
• Format: Journal Article
• Language: English
• Published: England John Wiley and Sons Inc 01.02.2018
• Subjects: G alpha 12; nuclear factor of activated T‐cell c1; Original; osteoclast; receptor activator of nuclear factor κB ligand; RhoA; G alpha 12; osteoclast; receptor activator of nuclear factor κB ligand; nuclear factor of activated T-cell c1; RhoA
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.13370

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.