Tatrai A, Foster S, Lakatos P, Shankar G, Stern P H
Department of Pharmacology, Northwestern University Medical School, Chicago, Illinois 60611.
Endocrinology. 1992 Aug;131(2):603-7. doi: 10.1210/endo.131.2.1639010.
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.
内皮素 -1（ET）对多种组织的作用是由前列腺素介导的。在本研究中，我们研究了ET对骨骼的作用，并确定其是否通过前列腺素依赖性途径介导。在新生小鼠颅骨和胎鼠肢体骨培养物中研究了骨吸收、胶原蛋白和非胶原蛋白合成以及肌醇磷酸（IP）生成。在存在或不存在环氧化酶抑制剂吲哚美辛（INDO）的情况下，检测ET在颅骨模型中的作用。ET刺激新生小鼠颅骨的骨吸收，而这种作用被INDO抑制。胎鼠肢体骨中的45Ca释放不受ET影响。在存在但不存在INDO的情况下，ET在颅骨模型中显著刺激胶原蛋白和非胶原蛋白合成，这表明ET的合成代谢作用被内源性前列腺素生成所掩盖。ET增加了两种骨器官培养物中的磷脂酰肌醇周转率。虽然添加INDO在小鼠颅骨中略微降低了IP生成，但它仍然受到ET的显著刺激。我们的结果表明，ET在体外对骨组织有显著影响。对骨吸收的影响似乎依赖于前列腺素，而合成代谢作用不是由前列腺素介导的。ET对蛋白质合成的刺激作用可能通过IP信号通路介导。由于ET刺激骨吸收和合成代谢，这种肽可能在骨重塑的耦联中起作用。
