Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice.
Absence of Cx43 selectively from osteocytes enhances responsiveness to mechanical force in mice.
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DOI：
10.1002/jor.22341
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发表时间：
2013-07
影响因子：
2.8
通讯作者：
Plotkin, Lilian I.
中科院分区：
文献类型：
--
作者：
Bivi, Nicoletta;Pacheco-Costa, Rafael;Brun, Lucas R.;Murphy, Thomas R.;Farlow, Nathan R.;Robling, Alexander G.;Bellido, Teresita;Plotkin, Lilian I.
骨细胞网络对骨对机械力的反应至关重要。在这个网络中，connexin43 （Cx43）被认为介导骨细胞和成骨细胞之间的通讯以及小分子与细胞外环境的交换。尽管最近在了解Cx43在骨细胞对机械刺激的反应中的作用方面取得了进展，但Cx43在骨细胞中对体内机械转导的特异性贡献尚不清楚。我们研究了骨细胞中缺乏Cx43的小鼠对尺向负荷的合成代谢反应（Cx43ΔOt）。与对照组相比，负载诱导Cx43ΔOt小鼠骨膜骨形成率的增加更大，这是由于更高的矿化表面和增强的矿物附着率。与对照组相比，Cx43ΔOt小鼠骨骼中β-连环蛋白（一种与机械转导有关的分子）的表达更高。此外，Cx43敲低的MLO-Y4骨细胞表现出更高的β-catenin蛋白表达和对机械刺激的反应增强。这些发现表明，缺乏Cx43的骨细胞会对机械刺激做出反应，而骨细胞中缺乏Cx43会通过一种可能涉及β-连环蛋白积累的机制释放骨形成。
The osteocyte network is crucial for the response of bone to mechanical force. Within this network, connexin43 (Cx43) is thought to mediate the communication of osteocytes and osteoblasts among themselves and the exchange of small molecules with the extracellular milieu. Despite recent advances in understanding Cx43 role for the response of bone cells to mechanical stimulation, the contribution of Cx43 specifically in osteocytes to mechanotransduction in vivo is not well-known. We examined the anabolic response to ulnar axial loading of mice lacking Cx43 in osteocytes (Cx43ΔOt). Loading induced a greater increase in periosteal bone formation rate in Cx43ΔOt mice compared to control littermates, resulting from higher mineralizing surface and enhanced mineral apposition rate. Expression of β-catenin protein, a molecule implicated in mechanotransduction, was higher in bones from Cx43ΔOt mice, compared to littermate controls. In addition, MLO-Y4 osteocytic cells knocked-down for Cx43 exhibited higher β-catenin protein expression and enhanced response to mechanical stimulation. These findings suggest that osteocytes lacking Cx43 are “primed” to respond to mechanical stimulation and that absence of Cx43 in osteocytes unleashes bone formation, by a mechanism that might involve accumulation of β-catenin.
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影响因子：
15.9
作者：
Plotkin, LI;Weinstein, RS;Bellido, T
通讯作者：
Bellido, T
影响因子：
6.2
作者：
Plotkin, Lilian I.;Lezcano, Virginia;Bellido, Teresita
通讯作者：
Bellido, Teresita
影响因子：
4.8
作者：
Gortazar, Arancha R.;Martin-Millan, Marta;Bellido, Teresita
通讯作者：
Bellido, Teresita
影响因子：
--
作者：
Jiang, JX;Cherian, PP
通讯作者：
Cherian, PP
影响因子：
6.2
作者：
Bivi, Nicoletta;Condon, Keith W.;Allen, Matthew R.;Farlow, Nathan;Passeri, Giovanni;Brun, Lucas R.;Rhee, Yumie;Bellido, Teresita;Plotkin, Lilian I.
通讯作者：
Plotkin, Lilian I.