Deficiency of the G-protein α-subunit Gsα in osteoblasts leads to differential effects on trabecular and cortical bone

Akio Sakamoto, Min Chen, Takashi Nakamura, Tao Xie, Gerard Karsenty, Lee S. Weinstein

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81 Citations (Scopus)


The G-protein α-subunit Gsα is required for the intracellular cAMP responses to hormones and other agonists. G sα is known to mediate the cAMP response to parathyroid hormone and other hormones and cytokines in bone and cartilage. To analyze the in vivo role of Gsα signaling in osteoblasts, we developed mice with osteoblast/osteocyte-specific Gsα deficiency (BGsKO) by mating Gsα-floxed mice with collagen Iα1 promoter-Cre recombinase transgenic mice. Early skeletal development was normal in BGsKO mice, because formation of the initial cartilage template and bone collar was unaffected. The chondrocytic zones of the growth plates also appeared normal in BGsKO mice. BGsKO mice had a defect in the formation of the primary spongiosa with reduced immature osteoid (new bone formation) and overall length, which led to reduced trabecular bone volume. In contrast, cortical bone was thickened with narrowing of the bone marrow cavity. This was probably due to decreased cortical bone resorption, because osteoclasts were markedly reduced on the endosteal surface of cortical bone. In addition, the expression of alkaline phosphatase, an early osteoblastic differentiation marker, was normal, whereas the expression of the late osteoblast differentiation markers osteopontin and osteocalcin was reduced, suggesting that the number of mature osteoblasts in bone is reduced. Expression of the osteoclast-stimulating factor receptor activator of NF-κB ligand was also reduced. Overall, our findings have similarities to parathyroid hormone null mice and confirm that the differential effects of parathyroid hormone on trabecular and cortical bone are primarily mediated via Gsα in osteoblasts. Osteoblast-specific G sα deficiency leads to reduced bone turnover.

Original languageEnglish
Pages (from-to)21369-21375
Number of pages7
JournalJournal of Biological Chemistry
Issue number22
Publication statusPublished - 2005 Jun 3
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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