| First Author | Ogata N | Year | 2011 |
| Journal | J Biol Chem | Volume | 286 |
| Issue | 15 | Pages | 13733-40 |
| PubMed ID | 21345793 | Mgi Jnum | J:171131 |
| Mgi Id | MGI:4948777 | Doi | 10.1074/jbc.M110.200196 |
| Citation | Ogata N, et al. (2011) G{alpha}q Signal in Osteoblasts Is Inhibitory to the Osteoanabolic Action of Parathyroid Hormone. J Biol Chem 286(15):13733-40 |
| abstractText | This study examined the role of the Galpha(q) signal constituted by Galpha(q) and Galpha(11) (encoded by Gnalpha(q) and Gnalpha(11), respectively), a major intracellular pathway of parathyroid hormone (PTH), in the PTH osteoanabolic action by the gain- and loss-of-function analyses. Transgenic mice with osteoblast-specific overexpression of the constitutively active Gnalpha(q) gene under the control of 2.3-kb type I collagen alpha1 chain (Col1a1) promoter exhibited osteopenia with decreased bone formation parameters and did not respond to the daily PTH treatment. We then established osteoblast-specific Gnalpha(q) and Gnalpha(11) double-knock-out (cDKO) mice by crossing the 2.3-kb Col1a1 promoter-Cre recombinase transgenic mice and those with Gnalpha(q) gene flanked with loxP and global ablation of Gnalpha(11) (Col1a1-Cre(+/-);Gna(q)(fl/fl);Gna(11)(-/-)) and found that the cDKO and single knock-out littermates of Gnalpha(q) or Gnalpha(11) exhibited normal bone volume and turnover under physiological conditions. With a daily injection of PTH, however, the cDKO mice, but not the single knock-out mice, showed higher bone volume and turnover than the wild-type littermates. Cultures of primary osteoblasts derived from cDKO and wild-type littermates confirmed enhancement of the PTH osteoanabolic action by the Galpha(q) signal deficiency in a cell-autonomous mechanism, in association with the membrane translocation of protein kinase Cdelta. This enhancement was reproduced by overexpression of regulator of G protein signaling-2, a Galpha(q) signal inhibitor, in osteoblastic MC3T3-E1 cells. Hence, the Galpha(q) signal plays an inhibitory role in the PTH osteoanabolic action, suggesting that its suppression may lead to a novel treatment in combination with PTH against osteoporosis. |
