Impaired osteoblast function in GPRC6A null mice

Min Pi, Lishu Zhang, Shu Feng Lei, Min Zhao Huang, Wenyu Zhu, Jianghong Zhang, Hui Shen, Hong Wen Deng, Leigh Quarles

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

GPRC6A is a widely expressed orphan G protein-coupled receptor that senses extracellular amino acids, osteocalcin, and divalent cations in vitro. GPRC6A null (GPRC6A-/-) mice exhibit multiple metabolic abnormalities including osteopenia. To investigate whether the osseous abnormalities are a direct function of GPRC6A in osteoblasts, we examined the function of primary osteoblasts and bone marrow stromal cell cultures (BMSCs) in GPRC6A -/- mice. We confirmed that GPRC6A-/- mice exhibited a decrease in bone mineral density (BMD) associated with reduced expression of osteocalcin, ALP, osteoprotegerin, and Runx2-II transcripts in bone. Osteoblasts and BMSCs derived from GPRC6A-/- mice exhibited an attenuated response to extracellular calcium-stimulated extracellular signal-related kinase (ERK) activation, diminished alkaline phosphatase (ALP) expression, and impaired mineralization ex vivo. In addition, siRNA-mediated knockdown of GPRC6A in MC3T3 osteoblasts also resulted in a reduction in extracellular calcium-stimulated ERK activity. To explore the potential relevance of GPRC6A function in humans, we looked for an association between GPRC6A gene polymorphisms and BMD in a sample of 1000 unrelated American Caucasians. We found that GPRC6A gene polymorphisms were significantly associated with human spine BMD. These data indicate that GRPC6A directly participates in the regulation of osteoblast-mediated bone mineralization and may mediate the anabolic effects of extracellular amino acids, osteocalcin, and divalent cations in bone.

Original languageEnglish (US)
Pages (from-to)1092-1102
Number of pages11
JournalJournal of Bone and Mineral Research
Volume25
Issue number5
DOIs
StatePublished - May 1 2010

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Osteoblasts
Osteocalcin
Bone Density
Divalent Cations
Mesenchymal Stromal Cells
Alkaline Phosphatase
Phosphotransferases
Cell Culture Techniques
Calcium
Multiple Abnormalities
Osteoprotegerin
Anabolic Agents
Amino Acids
Bone and Bones
Physiologic Calcification
Metabolic Bone Diseases
G-Protein-Coupled Receptors
Small Interfering RNA
Genes
Spine

All Science Journal Classification (ASJC) codes

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Impaired osteoblast function in GPRC6A null mice. / Pi, Min; Zhang, Lishu; Lei, Shu Feng; Huang, Min Zhao; Zhu, Wenyu; Zhang, Jianghong; Shen, Hui; Deng, Hong Wen; Quarles, Leigh.

In: Journal of Bone and Mineral Research, Vol. 25, No. 5, 01.05.2010, p. 1092-1102.

Research output: Contribution to journalArticle

Pi, M, Zhang, L, Lei, SF, Huang, MZ, Zhu, W, Zhang, J, Shen, H, Deng, HW & Quarles, L 2010, 'Impaired osteoblast function in GPRC6A null mice', Journal of Bone and Mineral Research, vol. 25, no. 5, pp. 1092-1102. https://doi.org/10.1359/jbmr.091037
Pi M, Zhang L, Lei SF, Huang MZ, Zhu W, Zhang J et al. Impaired osteoblast function in GPRC6A null mice. Journal of Bone and Mineral Research. 2010 May 1;25(5):1092-1102. https://doi.org/10.1359/jbmr.091037
Pi, Min ; Zhang, Lishu ; Lei, Shu Feng ; Huang, Min Zhao ; Zhu, Wenyu ; Zhang, Jianghong ; Shen, Hui ; Deng, Hong Wen ; Quarles, Leigh. / Impaired osteoblast function in GPRC6A null mice. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 5. pp. 1092-1102.
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