Increased bone mass in mice lacking the adipokine apelin.
Increased bone mass in mice lacking the adipokine apelin.
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DOI：
10.1210/en.2012-2034
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发表时间：
2013-04
期刊：
影响因子：
4.8
通讯作者：
L. Wattanachanya;Wei-Dar Lu;R. Kundu;Liping Wang;M. Abbott;Dylan O’Carroll;T. Quertermous;R. Nissenson
中科院分区：
文献类型：
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作者：
L. Wattanachanya;Wei-Dar Lu;R. Kundu;Liping Wang;M. Abbott;Dylan O’Carroll;T. Quertermous;R. Nissenson
脂肪组织在骨骼稳态中起着重要作用，并且有兴趣鉴定影响骨量的脂肪因子。一种这样的脂肪因子可以是爱帕琳，其是Gi-G蛋白偶联受体APJ的配体，已经报道其在MC 3 T3-E1细胞和原代人成骨细胞（OB）中增强有丝分裂发生并抑制细胞凋亡。然而，目前还不清楚爱帕琳是否在体内调节骨骼稳态中发挥生理作用。在这项研究中，我们比较了apelin基因敲除（APKO）和野生型小鼠的骨骼表型，并研究了apelin对体外骨细胞的直接影响。在12周龄时，在两种性别的APKO小鼠中观察到股骨远端松质骨体积分数增加，并持续至20岁。在两个时间点，雄性和雌性动物股骨中段的皮质骨周长均显著增加。动态组织形态计量学显示，APKO小鼠骨形成和矿物质沉积率增加，OB增殖和分化加速的证据，破骨细胞活性没有显着改变。一项体外研究表明，爱帕琳增加原代小鼠OB的增殖，并以剂量依赖性方式抑制细胞凋亡，最大效应为5 nM。但对矿化结核的形成没有影响。我们没有观察到破骨细胞参数在体外显着改变。总之，缺乏爱帕琳的小鼠中骨量增加表明爱帕琳对骨的复杂的直接和旁分泌/内分泌作用，可能通过调节胰岛素敏感性。这些结果表明，爱帕琳在体内骨中作为生理学上重要的抗合成代谢因子发挥作用。
Adipose tissue plays an important role in skeletal homeostasis, and there is interest in identifying adipokines that influence bone mass. One such adipokine may be apelin, a ligand for the Gi-G protein-coupled receptor APJ, which has been reported to enhance mitogenesis and suppress apoptosis in MC3T3-E1 cells and primary human osteoblasts (OBs). However, it is unclear whether apelin plays a physiological role in regulating skeletal homeostasis in vivo. In this study, we compared the skeletal phenotypes of apelin knockout (APKO) and wild-type mice and investigated the direct effects of apelin on bone cells in vitro. The increased fractional cancellous bone volume at the distal femur was observed in APKO mice of both genders at 12 weeks of age and persisted until the age of 20. Cortical bone perimeter at the femoral midshaft was significantly increased in males and females at both time points. Dynamic histomorphometry revealed that APKO mice had increased rates of bone formation and mineral apposition, with evidences of accelerated OB proliferation and differentiation, without significant alteration in osteoclast activity. An in vitro study showed that apelin increased proliferation of primary mouse OBs as well as suppressed apoptosis in a dose-dependent manner with the maximum effect at 5nM. However, it had no effect on the formation of mineralized nodules. We did not observed significantly altered in osteoclast parameters in vitro. Taken together, the increased bone mass in mice lacking apelin suggested complex direct and paracrine/endocrine effects of apelin on bone, possibly via modulating insulin sensitivity. These results indicate that apelin functions as a physiologically significant antianabolic factor in bone in vivo.