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缝隙连接细胞间通讯对MLO-Y4骨硬化蛋白和可溶性因子表达的影响

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

作者信息

York S L, Sethu P, Saunders M M

机构信息

Department of Biomedical Engineering, The University of Akron, Auburn Science and Engineering Center 275, West Tower, Akron, OH, 44325-0302, USA.

Department of Cardiovascular Disease, The University of Alabama at Birmingham, McCallum Basic Health Sciences Building 290 A, 1918 University Boulevard, Birmingham, AL, 35294, USA.

出版信息

Ann Biomed Eng. 2016 Apr;44(4):1170-80. doi: 10.1007/s10439-015-1376-6. Epub 2015 Jul 8.

Abstract

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.

摘要

骨重塑是一个持续的过程,在此过程中,破骨细胞吸收旧骨,成骨细胞形成新骨,为骨骼适应其力学环境变化的能力提供了一种机制。虽然成骨细胞和破骨细胞在骨重塑中的作用已得到充分了解,但骨重塑的细胞调节尚不清楚。一种理论认为,存在于骨内的骨细胞在控制骨重塑反应中起重要作用。骨细胞具有缝隙连接,即延伸至相邻细胞之间的狭窄通道,可通过小分子和离子的传递实现细胞间通讯。这项研究通过将类骨细胞MLO-Y4细胞暴露于机械应变下,并定量包括硬化蛋白(一种与骨重塑密切相关的蛋白质)在内的可溶性因子的表达,来研究缝隙连接细胞间通讯在骨重塑中的潜在作用。在抑制缝隙连接细胞间通讯后,进一步检测可溶性因子和硬化蛋白的表达,以研究该通讯的影响。在超生理应变下,与存在通讯的细胞相比,抑制缝隙连接细胞间通讯导致硬化蛋白表达增加,这表明该通讯可能在调节骨重塑中起重要作用。

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