Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures
Gap-junctional communication mediates parathyroid hormone stimulation of mineralization in osteoblastic cultures
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DOI：
10.1016/s8756-3282(00)00412-9
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发表时间：
2001-01-01
期刊：
影响因子：
4.1
通讯作者：
Howard, GA
中科院分区：
文献类型：
--
作者：
Schiller, PC;D'Ippolito, G;Howard, GA
以前，我们表明，生理水平的甲状旁腺激素（PTH）可以增加矿化的细胞外基质（ECM）的成骨样细胞在体外。在这项研究中，我们评估的作用，间隙连接细胞间通讯（GJC）在PTH增强矿化的ECM在MC 3 T3-E1细胞，小鼠培养模型的成骨细胞分化。MC 3 T3-E1间隙连接的主要成分连接蛋白43（Cx43）和GJC的信使RNA和蛋白随着细胞向成熟表型的进展而增加。免疫细胞化学显示Cx43在细胞之间的紧密接触区域积聚。在这些细胞中增加基质矿化的PTH处理的时间与Cx43和GJC的最高表达相一致。在培养期间的所有测试时间，18-α-大黄酸（阿加）的施用以剂量依赖性和可逆的方式迅速阻断了MC 3 T3-E1细胞培养物中的GJC。用阿加治疗，而不是用无活性的类似物，逆转PTH诱导的ECM矿化。这些数据表明，GJC介导与成骨细胞介导的矿化有关的PTH的合成代谢作用。(C)2001年，Elsevier Science Inc. All rights reserved.
Previously we showed that physiological levels of parathyroid hormone (PTH) can increase the mineralization of extracellular matrix (ECM) by osteoblast-like cells in vitro. In this study, we assess the role of gap-junctional intercellular communication (GJC) in the PTH-enhanced mineralization of ECM in MC3T3-E1 cells, a murine culture model of osteoblastic differentiation. Messenger RNA and protein for connexin 43 (Cx43), the major component of MC3T3-E1 gap junctions, and GJC increased as the cells progressed toward a mature phenotype, Immunocytochemistry showed accumulation of Cx43 at the area of close contact between cells. The timing of the PTH treatment that increased matrix mineralization in these cells coincided with the highest expression of Cx43 and GJC, Administration of 18-alpha -glycyrrhetinic acid (AGA) promptly blocked GJC in cultures of MC3T3-E1 cells in a dose-dependent and reversible manner at all times tested during the culture period. Treatment with AGA, but not with an inactive analog, reversed the PTH-induced ECM mineralization, These data suggest that GJC mediates anabolic actions of PTH related to osteoblast-mediated mineralization. (C) 2001 by Elsevier Science Inc. All rights reserved.