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Bone Abstracts (2016) 5 P150 | DOI: 10.1530/boneabs.5.P150

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Ben-Gurion University of the Negev, Beersheva, Israel.


G-protein coupled receptors (GPCRs) are the largest family of cell surface proteins, which are important for bone development, remodeling and diseases. One of the GPCRs, called GPR39, has been found to be expressed in several osteoblastic cell lines. However, its role in bone metabolism has not been investigated yet. In order to elucidate a role for GPR39, we characterized the bone phenotype in GPR39 deficient mice. During aging, at six months old, dynamic histomorphometry data reveal significant increase of mineralizing surface and bone formation rate in GPR39 deficient mice compared to wild type mice. Furthermore, we show by micro CT that bone mineral density of trabecular bone of femurs in GPR39 deficient mice is also significantly increased. Goldner’s Trichrome staining of undecalcified bone sections show significant increase in osteoblasts number and osteoid surface in GPR39 deficient mice, explaining higher rate of mineralization. Level of bone formation biomarker PINP is also significantly higher in GPR39 deficient mice, indicating an increase of bone formation. However, level of CTX-1 biomarker for bone resorption was significantly lower in GPR39 deficient mice. On the other hand, TRAP analysis show normal osteoclasts number and osteoclasts size in GPR39−/− bone sections. In vitro, bone marrow derived mesenchymal stem cells were differentiated into osteoblasts. Stainings of osteoblast culture show imbalance between bone matrix formation and mineralization, where Alizarin Red staining was higher and Collagen I staining lower in GPR39 deficient osteoblasts compared to wild type osteoblasts. mRNA expression analysis show enhanced expression levels of osteoblasts and osteocytes regulating genes in GPR39 deficient osteoblasts, suggesting that GPR39 negatively regulates osteoblast differentiation.

Our data reveal a novel role for GPR39 in regulation of bone metabolism and suggest that absence of GPR39 leads to enhanced bone formation.

Volume 5

43rd Annual European Calcified Tissue Society Congress

Rome, Italy
14 May 2016 - 17 May 2016

European Calcified Tissue Society 

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