| First Author | Wu M | Year | 2017 |
| Journal | Nat Commun | Volume | 8 |
| Pages | 13700 | PubMed ID | 28102206 |
| Mgi Jnum | J:244463 | Mgi Id | MGI:5913242 |
| Doi | 10.1038/ncomms13700 | Citation | Wu M, et al. (2017) Galpha13 negatively controls osteoclastogenesis through inhibition of the Akt-GSK3beta-NFATc1 signalling pathway. Nat Commun 8:13700 |
| abstractText | Many positive signalling pathways of osteoclastogenesis have been characterized, but negative signalling pathways are less well studied. Here we show by microarray and RNAi that guanine nucleotide-binding protein subunit alpha13 (Galpha13) is a negative regulator of osteoclastogenesis. Osteoclast-lineage-specific Gna13 conditional knockout mice have a severe osteoporosis phenotype. Gna13-deficiency triggers a drastic increase in both osteoclast number and activity (hyper-activation), mechanistically through decreased RhoA activity and enhanced Akt/GSK3beta/NFATc1 signalling. Consistently, Akt inhibition or RhoA activation rescues hyper-activation of Gna13-deficient osteoclasts, and RhoA inhibition mimics the osteoclast hyperactivation resulting from Gna13-deficiency. Notably, Galpha13 gain-of-function inhibits Akt activation and osteoclastogenesis, and protects mice from pathological bone loss in disease models. Collectively, we reveal that Galpha13 is a master endogenous negative switch for osteoclastogenesis through regulation of the RhoA/Akt/GSK3beta/NFATc1 signalling pathway, and that manipulating Galpha13 activity might be a therapeutic strategy for bone diseases. |
