Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation.
Cell autonomous requirement of connexin 43 for osteocyte survival: consequences for endocortical resorption and periosteal bone formation.
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DOI：
10.1002/jbmr.548
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发表时间：
2012-02
影响因子：
6.2
通讯作者：
Plotkin, Lilian I.
中科院分区：
文献类型：
--
作者：
Bivi, Nicoletta;Condon, Keith W.;Allen, Matthew R.;Farlow, Nathan;Passeri, Giovanni;Brun, Lucas R.;Rhee, Yumie;Bellido, Teresita;Plotkin, Lilian I.
关键词：
连接蛋白 43 (Cx43) 介导骨细胞与其他细胞和细胞外环境的通讯，并调节成骨细胞信号传导和基因表达。我们现在报道，成骨细胞/骨细胞中缺乏 Cx43 或仅在骨细胞中缺乏 Cx43 的小鼠（Cx43ΔOt 小鼠）表现出骨细胞凋亡、皮质内吸收和骨膜骨形成增加，导致在股骨中段骨干处测量到更高的骨髓腔和总组织面积。吸收阻断逆转了骨髓腔的增加，但没有逆转总组织面积，表明皮质内吸收和骨膜并置是独立调节的。凋亡骨细胞、骨细胞蛋白表达以及吸收和形成的解剖图表明，Cx43 通过分别调节位于皮质特定区域的骨细胞中的骨保护素和硬化素水平来控制破骨细胞和成骨细胞活性。在 Cx43ΔOt 小鼠中，空腔和缺乏骨保护素的活骨细胞分布在整个皮质骨中，而凋亡的骨细胞优先位于含有破骨细胞的区域，这表明破骨细胞的募集需要来自死亡骨细胞的活跃信号传导。此外，培养的骨细胞中Cx43缺失导致细胞凋亡增加和骨保护素表达减少。因此，Cx43 在体内和体外以细胞自主方式对于骨细胞存活和控制影响破骨细胞和成骨细胞功能的骨细胞基因的表达至关重要。
Connexin 43 (Cx43) mediates osteocyte communication with other cells and with the extracellular milieu and regulates osteoblastic cell signaling and gene expression. We now report that mice lacking Cx43 in osteoblasts/osteocytes or only in osteocytes (Cx43ΔOt mice) exhibit increased osteocyte apoptosis, endocortical resorption and periosteal bone formation, resulting in higher marrow cavity and total tissue areas measured at the femoral mid-diaphysis. Blockade of resorption reversed the increased marrow cavity but not total tissue area, demonstrating that endocortical resorption and periosteal apposition are independently regulated. Anatomical mapping of apoptotic osteocytes, osteocytic protein expression, and resorption and formation, suggests that Cx43 controls osteoclast and osteoblast activity by regulating osteoprotegerin and sclerostin levels, respectively, in osteocytes located in specific areas of the cortex. Whereas empty lacunae and living osteocytes lacking osteoprotegerin were distributed throughout cortical bone in Cx43ΔOt mice, apoptotic osteocytes were preferentially located in areas containing osteoclasts, suggesting that osteoclast recruitment requires active signaling from dying osteocytes. Furthermore, Cx43 deletion in cultured osteocytic cells resulted in increased apoptosis and decreased osteoprotegerin expression. Thus, Cx43 is essential in a cell-autonomous fashion in vivo and in vitro for osteocyte survival and for controlling the expression of osteocytic genes that affect osteoclast and osteoblast function.
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影响因子：
3.3
作者：
Cherian, PP;Siller-Jackson, AJ;Jiang, JX
通讯作者：
Jiang, JX
DOI：
10.1016/j.bbrc.2004.06.056
发表时间：
2004-08-06
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影响因子：
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作者：
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