Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.
Endothelin-1 actions on resorption, collagen and noncollagen protein synthesis, and phosphatidylinositol turnover in bone organ cultures.
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DOI：
10.1210/endo.131.2.1639010
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发表时间：
1992-08
期刊：
影响因子：
4.8
通讯作者：
A. Tatrai;Shirley A. Foster;P. Lakatos;G. Shankar;P. Stern
中科院分区：
文献类型：
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作者：
A. Tatrai;Shirley A. Foster;P. Lakatos;G. Shankar;P. Stern
内皮素-1（ET）对多种组织的作用是由洋地黄素介导的。在这项研究中，我们研究了ET对骨的作用，并确定它们是否通过依赖于肾上腺素的途径介导。在新生小鼠颅骨和胎鼠肢体骨培养中研究了骨吸收、胶原和非胶原蛋白合成以及磷酸肌醇（IP）的产生。在存在或不存在环氧化酶抑制剂吲哚美辛（INDO）的情况下，检查ET在颅骨模型中的作用。ET可刺激新生小鼠颅骨骨吸收，而INDO可抑制ET的这种作用。ET对胎鼠四肢骨中~（45）Ca释放无影响。ET刺激胶原蛋白和非胶原蛋白的合成显着的颅盖模型中的存在，但不是在没有INDO，这表明内源性前列腺素的产生掩盖了ET的合成代谢作用。ET增加磷脂酰肌醇营业额在两个骨器官培养。虽然INDO的加入略微降低了小鼠颅骨中IP的产生，但ET仍然显著刺激了IP的产生。结果表明，ET对体外骨组织有明显的作用。对吸收的影响似乎是前列腺素依赖性的，而合成代谢的影响不是前列腺素介导的。ET对蛋白质合成的刺激作用可能是通过IP信号通路介导的。由于ET刺激骨吸收和骨吸收，这种肽可能在骨重建的偶联中起作用。
The effects of endothelin-1 (ET) on several tissues are mediated by prostaglandins. In this study, we investigated the actions of ET on bone and determined whether they are mediated through prostaglandin-dependent pathways. Bone resorption, collagen, and non-collagen protein synthesis and inositol phosphate (IP) production were studied in neonatal mouse calvaria and fetal rat limb bone cultures. The effects of ET in the calvaria model were examined in the presence or absence of the cyclooxygenase inhibitor indomethacin (INDO). Bone resorption was stimulated by ET in the neonatal mouse calvaria, and this effect was inhibited by INDO. 45Ca release in the fetal rat limb bones was not affected by ET. ET stimulated collagen and noncollagen protein synthesis significantly in the calvaria model in the presence but not in the absence of INDO, suggesting that the anabolic effects of ET were masked by endogenous prostaglandin production. ET increased phosphatidylinositol turnover in both bone organ cultures. Although the addition of INDO reduced IP production slightly in the mouse calvaria, it was still significantly stimulated by ET. Our results demonstrate that ET has marked effects on bone tissue in vitro. Effects on resorption appear to be prostaglandin dependent, whereas the anabolic effects were not prostaglandin mediated. The stimulatory effects of ET on protein synthesis could be mediated through the IP signaling pathway. Since ET stimulates both bone resorption and anabolism, this peptide may have a role in the coupling of bone remodeling.