Osteocyte network; a negative regulatory system for bone mass augmented by the induction of Rankl in osteoblasts and Sost in osteocytes at unloading.
Osteocyte network; a negative regulatory system for bone mass augmented by the induction of Rankl in osteoblasts and Sost in osteocytes at unloading.
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DOI：
10.1371/journal.pone.0040143
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Komori T
中科院分区：
文献类型：
--
作者：
Moriishi T;Fukuyama R;Ito M;Miyazaki T;Maeno T;Kawai Y;Komori H;Komori T
机械应力降低是老年人骨质疏松症的主要原因，骨细胞网络，其中包括一个通信系统，通过过程和小管在整个骨，被认为是一个力学传感器和力学转导系统，然而，骨细胞的功能仍然是有争议的，仍然有待澄清。出乎意料的是，我们发现成骨细胞中BCL 2的过表达最终导致骨细胞凋亡。在体外，BCL 2转基因不影响成骨细胞和破骨细胞的分化。然而，皮质骨质量增加，由于增强成骨细胞功能和抑制破骨细胞在4个月龄时，TUNEL阳性骨陷窝的频率达到75%。在无负荷条件下，6周龄时野生型和BCL 2转基因小鼠的骨小梁骨量均下降，而4月龄时野生型小鼠的骨小梁骨量下降是由于成骨细胞功能受损和破骨细胞生成增强所致，而BCL 2转基因小鼠则不然。Rankl和Opg在骨细胞中高度表达，但在野生型小鼠中，在卸载时，Rankl在成骨细胞中的表达增加，而在骨细胞中的表达没有增加，但在4月龄的BCL 2转基因小鼠中没有增加。Sost在野生型小鼠中在卸载时被局部诱导，但在BCL 2转基因小鼠中没有，并且Sost的传播在BCL 2转基因小鼠中被严重中断，显示骨细胞网络严重受损。这些发现表明，在未加载条件下，成骨细胞中的Rankl和骨细胞中的Sost的上调需要骨细胞网络。这些发现表明，骨细胞网络通过抑制成骨细胞功能和激活破骨细胞生成来负调节骨量，并且这些功能在无负荷条件下至少部分地通过成骨细胞中Rankl表达和骨细胞中Sost表达的上调而增强，尽管不能排除成骨细胞中低BCL 2转基因表达有助于增强的成骨细胞功能。
Reduced mechanical stress is a major cause of osteoporosis in the elderly, and the osteocyte network, which comprises a communication system through processes and canaliculi throughout bone, is thought to be a mechanosensor and mechanotransduction system; however, the functions of osteocytes are still controversial and remain to be clarified. Unexpectedly, we found that overexpression of BCL2 in osteoblasts eventually caused osteocyte apoptosis. Osteoblast and osteoclast differentiation were unaffected by BCL2 transgene in vitro. However, the cortical bone mass increased due to enhanced osteoblast function and suppressed osteoclastogenesis at 4 months of age, when the frequency of TUNEL-positive lacunae reached 75%. In the unloaded condition, the trabecular bone mass decreased in both wild-type and BCL2 transgenic mice at 6 weeks of age, while it decreased due to impaired osteoblast function and enhanced osteoclastogenesis in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Rankl and Opg were highly expressed in osteocytes, but Rankl expression in osteoblasts but not in osteocytes was increased at unloading in wild-type mice but not in BCL2 transgenic mice at 4 months of age. Sost was locally induced at unloading in wild-type mice but not in BCL2 transgenic mice, and the dissemination of Sost was severely interrupted in BCL2 transgenic mice, showing the severely impaired osteocyte network. These findings indicate that the osteocyte network is required for the upregulation of Rankl in osteoblasts and Sost in osteocytes in the unloaded condition. These findings suggest that the osteocyte network negatively regulate bone mass by inhibiting osteoblast function and activating osteoclastogenesis, and these functions are augmented in the unloaded condition at least partly through the upregulation of Rankl expression in osteoblasts and that of Sost in osteocytes, although it cannot be excluded that low BCL2 transgene expression in osteoblasts contributed to the enhanced osteoblast function.
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影响因子：
6.2
作者：
Li, Xiaodong;Ominsky, Michael S.;Paszty, Chris
通讯作者：
Paszty, Chris
影响因子：
--
作者：
Bodine, PVN;Zhao, WG;Komm, BS
通讯作者：
Komm, BS
影响因子：
6.2
作者：
Lin, Chuwen;Jiang, Xuan;He, Lin
通讯作者：
He, Lin
影响因子：
4.1
作者：
Paic, Frane;Igwe, John C.;Nori, Ravi;Kronenberg, Mark S.;Franceschetti, Tiziana;Harrington, Patrick;Kuo, Lynn;Shin, Dong-Guk;Rowe, David W.;Harris, Stephen E.;Kalajzic, Ivo
通讯作者：
Kalajzic, Ivo
影响因子：
4
作者：
Moustafa, A.;Sugiyama, T.;Prasad, J.;Zaman, G.;Gross, T. S.;Lanyon, L. E.;Price, J. S.
通讯作者：
Price, J. S.