Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption

Death of osteocytes turns off the inhibition of osteoclasts and triggers local bone resorption
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DOI:
10.1016/j.bbrc.2005.06.211
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发表时间:
2005-10-07
影响因子:
3.1
通讯作者:
Väänänen, HK
Väänänen, HK
中科院分区:
生物学4区
文献类型:
--
作者:
Gu, GL;Mulari, M;Väänänen, HK

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骨细胞被认为在骨吸收的调节中发挥作用,尽管它们对骨转换的影响仍然存在争议。为了研究这一问题,我们建立了一个基于离体大鼠颅骨的器官培养系统,在该系统中可以监测骨细胞的活力及其对骨细胞骨吸收的影响。我们的研究结果表明,骨细胞是组成性的负调节骨细胞活性。破骨细胞在颅骨切片上培养,里面有活的骨细胞,不能形成肌动蛋白环,而肌动蛋白环是吸收细胞的标志。从颅骨器官培养获得的条件培养基也实现了类似的抑制作用,表明活骨细胞产生尚未识别的破骨细胞抑制剂。相反,当诱导骨细胞凋亡时,这种抑制作用消失,并观察到强烈的骨细胞骨吸收活性。因此,骨细胞的局部凋亡可能在触发局部骨重建中起主要作用。(c)2005年爱思唯尔公司All rights reserved.
Osteocytes have been suggested to play a role in the regulation of bone resorption, although their effect on bone turnover has remained controversial. In order to study this open question, we developed an organ culture system based on isolated rat calvaria, where the osteocyte viability and its effect on osteoclastic bone resorption can be monitored. Our results suggest that osteocytes are constitutively negative regulators of osteoclastic activity. Osteoclasts, which were cultured on calvarial slices with living osteocytes inside, failed to form actin rings which are the hallmarks of resorbing cells. A similar inhibitory effect was also achieved by the conditioned medium obtained from calvarial organ culture, suggesting that living osteocytes produce yet unrecognized osteoclast inhibitors. On the contrary, when osteocyte apoptosis was induced, this inhibitory effect disappeared and strong osteoclastic bone resorption activity was observed. Thus, local apoptosis of osteocytes may play a major role in triggering local bone remodeling. (c) 2005 Elsevier Inc. All rights reserved.