Impact of Gap Junctional Intercellular Communication on MLO-Y4 Sclerostin and Soluble Factor Expression.

Impact of Gap Junctional Intercellular Communication on MLO-Y4 Sclerostin and Soluble Factor Expression.
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DOI:
10.1007/s10439-015-1376-6
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发表时间:
2016-04
影响因子:
3.8
通讯作者:
Saunders MM
Saunders MM
中科院分区:
工程技术2区
文献类型:
--
作者:
York SL;Sethu P;Saunders MM

文献摘要

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骨重塑是一个持续的过程,其中旧骨被破骨细胞吸收,新骨由成骨细胞形成,为骨骼适应机械环境变化的能力提供了机制。虽然成骨细胞和破骨细胞在骨重塑中的作用已被充分了解,但骨重塑的细胞调节尚不清楚。一种理论认为,骨内的骨细胞在控制骨重塑反应中发挥着重要作用。骨细胞具有间隙连接,即在附近细胞之间延伸的狭窄通道,并允许细胞之间通过小分子和离子的转移进行通讯。这项工作通过将骨细胞样 MLO-Y4 细胞暴露于机械应变并量化可溶性因子(包括硬化蛋白(一种与骨重塑密切相关的蛋白质)的表达),研究了间隙连接细胞间通讯在骨重塑中的潜在作用。抑制间隙连接细胞间通讯后,进一步检测可溶性因子和硬化素表达,以研究通讯的影响。在超生理应变下,间隙连接细胞间通讯的抑制导致硬化素表达相对于存在通讯的细胞增加,表明通讯可能在调节骨重塑中发挥重要作用。
Bone remodeling is a continual process in which old bone is resorbed by osteoclasts and new bone is formed by osteoblasts, providing a mechanism for bones’ ability to adapt to changes in its mechanical environment. While the role of osteoblasts and osteoclasts in bone remodeling is well understood, the cellular regulation of bone remodeling is unclear. One theory is that osteocytes, found within bone, play an important role in controlling the bone remodeling response. Osteocytes possess gap junctions, narrow channels that extend between nearby cells and allow communication between cells via the transfer of small molecules and ions. This work investigated the potential role of gap junctional intercellular communication in bone remodeling by exposing osteocyte-like MLO-Y4 cells to mechanical strains and quantifying the expression of soluble factors, including sclerostin, a protein closely associated with bone remodeling. The soluble factors and sclerostin expression were further examined after inhibiting gap junctional intercellular communication to study the impact of the communication. At supraphysiologic strains, the inhibition of gap junctional intercellular communication led to increases in sclerostin expression relative to cells in which communication was present, indicating that the communication may play a significant role in regulating bone remodeling.