Lin Yuan Yu, Chen Ching Yi, Chuang Tai Yuan, Lin Yun, Liu Hui Yu, Mersmann Harry John, Wu Shinn Chih, Ding Shih Torng
Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan.
Department of Athletics, National Taiwan University, Taipei, Taiwan.
Bone. 2014 Jul;64:147-54. doi: 10.1016/j.bone.2014.03.051. Epub 2014 Apr 5.
Adiponectin and its receptors are expressed in bone marrow-derived osteoblasts. Previous studies in vivo and in vitro have produced controversial results. The purpose of this study was to use porcine adiponectin receptor 1 transgenic mice (pAdipoR1) as a model to evaluate the role of AdipoR1 on bone physiology at different ages. pAdipoR1 transgenic mice had higher bone mineral density than wild-type mice in both genders at 56 weeks of age. The bone volume and trabecular number, measured by micro-computed tomography (μCT) was significantly greater in transgenic than in wild-type female mice at both 8 and 56 weeks of age. ELISA analysis revealed that both serum osteocalcin and osteoprotegerin (OPG) were significantly increased in 8-week old pAdipoR1 transgenic mice of both genders. Furthermore, serum OPG was elevated at 32 and 56 weeks of age in female and male pAdipoR1 transgenic mice. Serum TRAP5b concentration was reduced in 8 and 56 weeks old male pAdipoR1 mice compared with wild-type male mice. Knock-down of AdipoR1 significantly decreased gene expression of osteocalcin, OPG, alkaline phosphatase and msh homeobox 2 and the mineralization in MC3T3-E1 cells and mesenchymal stem cells. In addition, pathscan analysis and real-time PCR analysis suggest AdipoR1 regulates osteoblast differentiation through GSK-3 β and β-Catenin signaling. Consequently, the lack of AdipoR1 impaired osteoblast differentiation and bone formation. We conclude that AdipoR1 is a critical factor for the osteoblast differentiation and bone homeostasis.
脂联素及其受体在骨髓来源的成骨细胞中表达。先前的体内和体外研究产生了有争议的结果。本研究的目的是使用猪脂联素受体1转基因小鼠（pAdipoR1）作为模型，评估AdipoR1在不同年龄对骨骼生理的作用。56周龄时，pAdipoR1转基因小鼠无论雌雄，其骨密度均高于野生型小鼠。通过显微计算机断层扫描（μCT）测量，在8周龄和56周龄时，转基因雌性小鼠的骨体积和骨小梁数量均显著高于野生型雌性小鼠。ELISA分析显示，8周龄的pAdipoR1转基因小鼠无论雌雄，血清骨钙素和骨保护素（OPG）均显著升高。此外，在32周龄和56周龄时，pAdipoR1转基因雌性和雄性小鼠的血清OPG均升高。与野生型雄性小鼠相比，8周龄和56周龄的雄性pAdipoR1小鼠血清TRAP5b浓度降低。敲低AdipoR1可显著降低MC3T3-E1细胞和间充质干细胞中骨钙素、OPG、碱性磷酸酶和msh同源盒2的基因表达以及矿化。此外，通路扫描分析和实时PCR分析表明，AdipoR1通过GSK-3β和β-连环蛋白信号传导调节成骨细胞分化。因此，缺乏AdipoR1会损害成骨细胞分化和骨形成。我们得出结论，AdipoR1是成骨细胞分化和骨稳态的关键因素。
