Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass
Osteocalcin is necessary for the alignment of apatite crystallites, but not glucose metabolism, testosterone synthesis, or muscle mass
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DOI：
10.1371/journal.pgen.1008586
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发表时间：
2020-05-01
期刊：
影响因子：
4.5
通讯作者：
Komori, Toshihisa
中科院分区：
文献类型：
--
作者：
Moriishi, Takeshi;Ozasa, Ryosuke;Komori, Toshihisa
骨的强度取决于骨的数量和质量。骨钙素（OCN）是骨中最丰富的非胶原蛋白，由成骨细胞产生。之前已经声称OCN抑制骨形成，并且还作为一种激素来调节胰腺中的胰岛素分泌、睾丸中的睾酮合成和肌肉质量。我们通过删除Bglap和Bglap 2产生了Ocn缺陷型（Ocn（-/-））小鼠。对OCN（-/-）小鼠的分析表明，OCN不参与骨量、葡萄糖代谢、睾酮合成或肌肉质量的调节。Ocn（-/-）骨中胶原纤维的取向度和c轴上生物磷灰石（BAp）微晶的尺寸正常。然而，通常平行于胶原纤维的BAp c轴的晶体学取向被严重破坏，导致骨强度降低。这些结果表明，OCN是需要通过调整BAp微晶平行于胶原纤维的排列骨质量和强度;但它不作为一种hormone.Author summaryThe强度的骨取决于它的数量和质量。骨钙素（OCN）是骨中含量最丰富的非胶原蛋白，但其功能尚不清楚。其他研究人员的早期研究表明，OCN通过减少骨形成来减少骨量;此外，它还可以作为一种激素来调节葡萄糖代谢，睾酮合成和远处组织中的肌肉质量。我们已经产生了Ocn缺陷型小鼠，并在本文中显示Ocn不是骨形成所必需的。然而，这是最佳骨质和强度所必需的。具体来说，我们表明，在OCN缺陷小鼠胶原纤维正常对齐，但磷灰石微晶对齐随机对胶原蛋白，导致矿化紊乱和骨强度降低。此外，我们表明，葡萄糖代谢，睾酮合成和肌肉质量是正常的OCN缺陷小鼠。我们得出结论，OCN在骨中起作用，以优化其质量和强度，而不是数量。而且，与早期的说法相反，它不能作为激素来控制葡萄糖代谢、睾酮合成和肌肉质量。
The strength of bone depends on bone quantity and quality. Osteocalcin (Ocn) is the most abundant noncollagenous protein in bone and is produced by osteoblasts. It has been previously claimed that Ocn inhibits bone formation and also functions as a hormone to regulate insulin secretion in the pancreas, testosterone synthesis in the testes, and muscle mass. We generated Ocn-deficient (Ocn(-/-)) mice by deleting Bglap and Bglap2. Analysis of Ocn(-/-)mice revealed that Ocn is not involved in the regulation of bone quantity, glucose metabolism, testosterone synthesis, or muscle mass. The orientation degree of collagen fibrils and size of biological apatite (BAp) crystallites in the c-axis were normal in the Ocn(-/-)bone. However, the crystallographic orientation of the BAp c-axis, which is normally parallel to collagen fibrils, was severely disrupted, resulting in reduced bone strength. These results demonstrate that Ocn is required for bone quality and strength by adjusting the alignment of BAp crystallites parallel to collagen fibrils; but it does not function as a hormone.Author summaryThe strength of bone depends on both its quantity and quality. Osteocalcin (Ocn) is the most abundant non-collagenous protein in bone, but its function remains unclear. Earlier studies by other investigators have suggested that Ocn decreases the quantity of bone by decreasing bone formation; and in addition it works as a hormone to regulate glucose metabolism, testosterone synthesis, and muscle mass in distant tissues. We have generated Ocn-deficient mice and show herein that Ocn is not required for bone formation. It is, however, required for optimal bone quality and strength. Specifically, we show that in the Ocn-deficient mice collagen fibers align normally, but apatite crystallites align randomly against collagen, resulting in disorganized mineralization and reduced bone strength. Furthermore, we show that glucose metabolism, testosterone synthesis, and muscle mass are normal in the Ocn-deficient mice. We conclude that Ocn acts in bone to optimize its quality and strength, but not quantity. And, in contrast to earlier claims, it does not work as a hormone to control glucose metabolism, testosterone synthesis, and muscle mass.