Mechanical load regulates bone growth via periosteal Osteocrin
Mechanical load regulates bone growth via periosteal Osteocrin
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DOI：
10.1016/j.celrep.2021.109380
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发表时间：
2021-07-13
期刊：
影响因子：
8.8
通讯作者：
Mochizuki, Naoki
中科院分区：
文献类型：
--
作者：
Watanabe-Takano, Haruko;Ochi, Hiroki;Mochizuki, Naoki
机械刺激，包括出生后的负荷，促进骨骼生长。然而，很少有人知道机械力如何触发生化信号来调节骨生长。在这里，我们确定了骨膜成骨细胞来源的分泌肽，骨蛋白（Osteocrin），作为一个机械传感器参与负荷诱导的长骨生长。骨膜成骨细胞产生的骨钙素通过增强C型利钠肽（CNP）依赖性的软骨细胞增殖和成熟来调节生长板生长，导致长骨伸长。此外，ODN与CNP合作调节骨形成。CNP刺激骨膜骨祖细胞的成骨分化以诱导骨形成。骨钙素与骨膜骨祖细胞中的利钠肽受体3（NPR3）结合，从而阻止NPR3介导的CNP清除，从而促进CNP信号介导的骨生长。重要的是，生理负荷通过抑制Forkhead box蛋白O1（FoxO1）转录因子诱导骨膜成骨细胞中的OX3表达。因此，这项研究揭示了一个至关重要的作用，骨钙素作为一个mechanotransducer转换机械负荷的CNP依赖性骨形成。
Mechanical stimuli including loading after birth promote bone growth. However, little is known about how mechanical force triggers biochemical signals to regulate bone growth. Here, we identified a periosteal-osteoblast-derived secretory peptide, Osteocrin (OSTN), as a mechanotransducer involved in load-induced long bone growth. OSTN produced by periosteal osteoblasts regulates growth plate growth by enhancing C-type natriuretic peptide (CNP)-dependent proliferation and maturation of chondrocytes, leading to elongation of long bones. Additionally, OSTN cooperates with CNP to regulate bone formation. CNP stimulates osteogenic differentiation of periosteal osteoprogenitors to induce bone formation. OSTN binds to natriuretic peptide receptor 3 (NPR3) in periosteal osteoprogenitors, thereby preventing NPR3-mediated clearance of CNP and consequently facilitating CNP-signal-mediated bone growth. Importantly, physiological loading induces Ostn expression in periosteal osteoblasts by suppressing Forkhead box protein O1 (FoxO1) transcription factor. Thus, this study reveals a crucial role of OSTN as a mechanotransducer converting mechanical loading to CNP-dependent bone formation.