Department of Cellular Physiological Chemistry, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo 113-8549, Japan.
J Endocrinol. 2010 Feb;204(2):125-33. doi: 10.1677/JOE-09-0376. Epub 2009 Nov 11.
Prostaglandins (PGs) are key regulatory factors that affect bone metabolism. Prostaglandin E(2) (PGE(2)) regulates bone resorption and bone formation. Prostacyclin (PGI(2)) is one of the major products derived from arachidonic acid by the action of cyclooxygenase and PGI(2) synthase (PGIS). Unlike PGE(2), there are few reports about the role of PGI(2) in bone regulation. Therefore, we investigated the potential effect of PGI(2) on bone metabolism. We used PGIS knockout (PGIS(-/-)), PGIS heterozygous (PGIS(+)(/-)), and wild-type mice to investigate the role of PGI(2). Notably, PGIS(-/-) mice gradually displayed an increase in trabecular bone mass in adolescence. Adult PGIS(-/-) mice showed an increase in trabecular bone volume/tissue volume. Histomorphometric analysis showed that PGIS(-/-) mice displayed increases in both bone formation and bone resorption parameters. Levels of serum osteocalcin and C-telopeptides were increased in adult PGIS(-/-) mice. Furthermore, the increased bone mass patterns were rescued in PGIS(-)/(tg) mice. In conclusion, adult PGIS(-/-) mice displayed an overall increase in the levels of both bone formation and bone resorption parameters, which suggests that PGI(2) deficiency accelerates high bone turnover activity with a greater increase in bone mass in aging. These results indicated that PGI(2) may contribute to the maintenance of normal bone mass and micro-architecture in mice in age-dependent manner. Our findings demonstrate for the first time that PGI(2) is involved in bone metabolism in vivo.
前列腺素（PGs）是影响骨代谢的关键调节因子。前列腺素 E2（PGE2）调节骨吸收和骨形成。前列环素（PGI2）是花生四烯酸经环加氧酶和 PGI2 合酶（PGIS）作用产生的主要产物之一。与 PGE2 不同，关于 PGI2 在骨调节中的作用的报道较少。因此，我们研究了 PGI2 对骨代谢的潜在影响。我们使用 PGIS 敲除（PGIS(-/-)）、PGIS 杂合（PGIS(+/-)）和野生型小鼠来研究 PGI2 的作用。值得注意的是，PGIS(-/-) 小鼠在青春期逐渐表现出骨小梁骨量增加。成年 PGIS(-/-) 小鼠的骨小梁体积/组织体积增加。组织形态计量学分析显示，PGIS(-/-) 小鼠的骨形成和骨吸收参数均增加。成年 PGIS(-/-) 小鼠的血清骨钙素和 C 端肽水平升高。此外，PGIS(-)/(tg) 小鼠的增加骨量模式得到挽救。总之，成年 PGIS(-/-) 小鼠的骨形成和骨吸收参数水平整体增加，表明 PGI2 缺乏加速了衰老时高骨转换活性，骨量增加更大。这些结果表明，PGI2 可能以依赖年龄的方式有助于维持小鼠正常的骨量和微结构。我们的研究结果首次表明 PGI2 参与体内骨代谢。
