Investigation of bioeffects of G protein-coupled receptor 1 on bone turnover in male mice.
Investigation of bioeffects of G protein-coupled receptor 1 on bone turnover in male mice.
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G蛋白偶联受体1对雄性小鼠骨转换的生物效应研究
DOI：
10.1016/j.jot.2017.05.001
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发表时间：
2017-07
影响因子：
6.6
通讯作者：
Ren PG
中科院分区：
文献类型：
--
作者：
Li J;Xiang L;Jiang X;Teng B;Sun Y;Chen G;Chen J;Zhang JV;Ren PG
维持健康的骨质量和数量需要成骨细胞的骨形成和破骨细胞的骨吸收之间的良好协调平衡。Chemerin是一种新的脂肪细胞因子，具有通过激活趋化因子样受体1（CMKLR 1）调节免疫和能量平衡等功能。G蛋白偶联受体1（GPR 1）是第二种与CMKLR 1具有相似结合亲和力的哺乳动物趋化素受体。在雄性GPR 1-/-小鼠中，观察到骨矿物质密度显著降低的表型。我们推测GPR 1可能参与了骨重建的过程。在这项研究中，我们研究了GPR 1在调节雄性小鼠骨量维持中的作用，并首次发现，与野生型动物相比，GPR 1-/-雄性小鼠表现出严重的骨小梁丢失和较低的血清睾酮水平。因此，与成骨细胞[I型胶原α 2（Col 1A 2）、骨钙素（OCN）]和破骨细胞[抗酒石酸酸性磷酸酶（TRAP）、组织蛋白酶K、NFATc 1]相关的生物标志物的mRNA表达在GPR 1-/-小鼠中相对于野生型分别显著降低或升高。然而，其他成骨标志物Osterix和ALP水平升高。显微计算机断层扫描和组织学分析证明，在GPR 1-/-小鼠中存在大量的骨小梁丢失。与此同时，GPR 1-/-小鼠的血清睾酮水平显着下降。综上所述，这些发现表明chemerin-GPR 1信号转导可能直接或间接地与睾酮合成在骨转换调节中沟通。需要进一步详细的研究来揭示chemerin-GPR 1如何参与骨代谢。本文的翻译潜力：对GPR 1在骨转换中调控功能的进一步研究和认识，可能为骨质疏松症的治疗提供新的靶点。
Maintenance of healthy bone quality and quantity requires a well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. Chemerin is a novel adipokine with known functions such as regulating immunity and energy homeostasis through activation of chemokine-like receptor 1 (CMKLR1). G protein-coupled receptor 1 (GPR1) is the second mammalian chemerin receptor with similar binding affinity as CMKLR1. In male GPR1–/– mice, a phenotype with significantly low bone mineral density was observed. We hypothesise that GPR1 might participate the process of bone remodelling. In this study, we investigated the role of GPR1 in regulating bone mass maintenance in male mice, and for the first time, revealed that GPR1–/– male mice manifested seriously trabecular bone loss and lower serum testosterone levels compared to the wild type animals. Accordingly, the mRNA expression of biomarkers related to both osteoblast [collagen type I alpha 2 (Col1A2), osteocalcin (OCN)] and osteoclast [tartrate-resistant acid phosphatase (TRAP), Cathepsin K, NFATc1] were significantly decreased or increased in GPR1–/– mice relative to the wild type, respectively. However, other osteogenic markers, Osterix and ALP levels, were increased. Microcomputed tomography scanning and histological analyses proved that there was a myriad of trabecular bone loss in GPR1–/– mice. In the meantime, GPR1–/– mice presented a significant decrease in serum testosterone level. Taken together, these findings suggested that chemerin–GPR1 signalling might be directly or indirectly communicated with testosterone synthesis on bone turnover regulation. Further detailed studies are required to unveil how chemerin–GPR1 participates in bone metabolism. The translational potential of this article: More studies and knowledge about GPR1 regulating function in bone turnover might supply a novel therapeutic target for osteoporosis in the future.
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影响因子：
4.9
作者：
Lane NE;Yao W
通讯作者：
Yao W
影响因子：
3.9
作者：
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通讯作者：
Sibirny, Andriy A.
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Chung, Hwa-Jin;Kim, Won Kyung;Lee, Sang Kook
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