Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading
Osteocytes as mechanosensors in the inhibition of bone resorption due to mechanical loading
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DOI：
10.1016/j.bone.2007.09.047
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发表时间：
2008-01-01
期刊：
影响因子：
4.1
通讯作者：
Jacobs, Christopher R.
中科院分区：
文献类型：
--
作者：
You, Lidan;Temiyasathit, Sara;Jacobs, Christopher R.
骨具有调整其结构以适应其力学环境的能力。骨机械生物学的主流观点是骨细胞负责检测和响应机械载荷并启动骨适应过程。然而，骨细胞如何向效应细胞发出信号并启动骨转换尚不清楚。最近的体外研究表明，当与破骨细胞前体共培养时，骨细胞支持破骨细胞的形成和活化。本研究旨在探讨骨细胞在破骨细胞形成和活化的机械调节中的作用，结果表明：（1）机械刺激MLO-Y 4类骨细胞与RAW264.7单核细胞破骨细胞前体共培养时，其破骨支持能力降低;（2）这些机械刺激的MLO-Y 4细胞释放的可溶性因子抑制ST 2骨髓基质细胞或MLO-Y 4细胞诱导的破骨细胞生成;（3）MLO-Y 4细胞释放可溶性RANKL和OPG，两者的表达受机械负荷的调节，提示机械负荷降低了骨细胞通过细胞-细胞直接接触诱导破骨细胞形成的能力。然而，目前尚不清楚体内骨细胞是否能够与破骨细胞前体形成接触。我们的数据还表明，机械刺激骨细胞释放可溶性因子，可以抑制破骨细胞诱导的其他支持细胞，包括骨髓基质细胞。综上所述，我们得出结论，骨细胞可能通过可溶性信号调节局部破骨细胞的生成，起到机械换能器的作用。(C)2007爱思唯尔公司All rights reserved.
Bone has the ability to adjust its structure to meet its mechanical environment. The prevailing view of bone mechanobiology is that osteocytes are responsible for detecting and responding to mechanical loading and initiating the bone adaptation process. However, how osteocytes signal effector cells and initiate bone turnover is not well understood. Recent in vitro studies have shown that osteocytes support osteoclast formation and activation when co-cultured with osteoclast precursors. In this study, we examined the osteocytes' role in the mechanical regulation of osteoclast formation and activation.We demonstrated here that (1) mechanical stimulation of MLO-Y4 osteocyte-like cells decreases their osteoclastogenic-support potential when co-cultured with RAW264.7 monocyte osteoclast precursors; (2) soluble factors released by these mechanically stimulated MLO-Y4 cells inhibit osteoclastogenesis induced by ST2 bone marrow stromal cells or MLO-Y4 cells; and (3) soluble RANKL and OPG were released by MLO-Y4 cells, and the expressions of both were found to be mechanically regulated.Our data suggest that mechanical loading decreases the osteocyte's potential to induce osteoclast formation by direct cell-cell contact. However, it is not clear that osteocytes in vivo are able to form contacts with osteoclast precursors. Our data also demonstrate that mechanically stimulated osteocytes release soluble factors that can inhibit osteoclastogenesis induced by other supporting cells including bone marrow stromal cells. In summary, we conclude that osteocytes may function as mechanotransducers by regulating local osteoclastogenesis via soluble signals. (C) 2007 Elsevier Inc. All rights reserved.