ANTI-OSTEOPOROTIC ACTIONS OF ESTROGENS

雌激素的抗骨质疏松作用

• 批准号: 5210015
• 负责人: Keith L Kirkwood
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5210015
• 关键词: cytokine; estradiol; genetic regulation; genetic transcription; hormone regulation /control mechanism; inositol phosphates; osteoblasts; osteoporosis; parathyroid hormones; physiologic bone resorption; prostaglandin E; receptor expression; tissue /cell culture; vitamin D receptors

The inositol trisphosphate receptor (IP3R) is an intracellular calcium channel that mediates the cellular actions of many hormones, growth factors, and cytokines. In osteoblastic cell cultures, many bone resorbing hormones increase inositol trisphosphate production, mobilization of intracellular calcium, and secretion of osteoclast recruitment and activating factors. The effects of 17B-estradiol, 1,25-dihydroxyvitamin D3, phorbol esters and serum on IP3R mRNA levels were evaluated in osteogenic-osteosarcoma cells (G-292, U-2 OS, Saos-2, MC3T3-El and UMR-106) and in primary osteoblastic cultures derived from neonatal rat calvaria. Type specific RT-PCR indicated that all cell types evaluated express IP3R mRNA type I; G-292, U-2 OS, MC3T3-El, and calvarial osteoblastic cells express type II IP3R mRNA; and UMR-106 and the calvarial osteoblastic cells express type III IP3R gene. Northern blot analysis indicated that phorbol ester and serum increase steady state IP3R mRNA expression in G-292 cells and in calvarial osteoblastic cells. Further characterization of IP3R gene expression in G-292 cells indicated that 17B-estradiol and 1,25-dihydroxyvitamin D3 decrease IP3R mRNA levels. The effect of 17B-estradiol was not due to accelerated IP3R mRNA degradation and required continued protein synthesis. The results indicate that IP3R expression in osteoblastic osteosarcoma cells is affected by 17B-estradiol and other osteoporotic and anti-osteoporotic hormones and may be important in the chronic regulation of osteoblast secretory activity.

肌醇三磷酸受体（IP3R）是 介导许多细胞作用的细胞内钙通道 激素，生长因子和细胞因子。 在成骨细胞培养物中， 许多骨吸收激素会增加肌醇三磷酸盐的产生， 动员细胞内钙和破骨细胞的分泌 招募和激活因素。 17b-雌二醇的影响， 1,25-二羟基维生素D3，佛波酯和IP3R mRNA水平的血清 在成骨稳定性细胞中评估（G-292，U-2 OS，Saos-2， MC3T3-EL和UMR-106）以及源自原始成骨细胞培养物。 新生儿大鼠瓦尔瓦里亚。 类型特定的RT-PCR表明所有单元格 评估了Express IP3R mRNA I型； G-292，U-2 OS，MC3T3-EL和钙 成骨细胞表达II型IP3R mRNA；和UMR-106和 钙化成骨细胞表达III型IP3R基因。 北印迹 分析表明凤凰酯和血清增加稳态IP3R G-292细胞和钙化成骨细胞细胞中的mRNA表达。 G-292细胞中IP3R基因表达的进一步表征 17b-雌二醇和1,25-二羟基维生素D3降低了IP3R mRNA水平。 17b-雌二醇的效果不是由于加速IP3R mRNA引起的 降解并需要持续的蛋白质合成。 结果 表明在成骨细胞骨肉瘤细胞中的IP3R表达是 受17b-雌二醇和其他骨质疏松性和抗抑制性疏松性的影响 激素，可能在成骨细胞的慢性调节中很重要 分泌活动。