Journal article
Loss of Gsα in the postnatal skeleton leads to low bone mass and a blunted response to anabolic parathyroid hormone therapy
P Sinha, P Aarnisalo, R Chubb, IJ Poulton, J Guo, G Nachtrab, T Kimura, S Swami, H Saeed, M Chen, LS Weinstein, E Schipani, NA Sims, HM Kronenberg, JY Wu
Journal of Biological Chemistry | AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC | Published : 2016
Abstract
Parathyroid hormone (PTH) is an important regulator of osteoblast function and is the only anabolic therapy currently approved for treatment of osteoporosis. The PTH receptor (PTH1R) is a G protein-coupled receptor that signals via multiple G proteins including Gsα. Mice expressing a constitutively active mutant PTH1R exhibited a dramatic increase in trabecular bone that was dependent upon expression of Gsα in the osteoblast lineage. Postnatal removal of Gsα in the osteoblast lineage (P-GsαOsxKO mice) yielded markedly reduced trabecular and cortical bone mass. Treatment with anabolic PTH(1-34) (80 μg/kg/day) for 4 weeks failed to increase trabecular bone volume or cortical thickness in male ..
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Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by National Institutes of Health Grants AR054741 and AR059942 (to J. Y. W.), AR061228 (to P. S.), and DK011794 (to H. M. K.) and the NIDDK Intramural Research Program (to M. C. and L. S. W.). The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.