Prostaglandins (PGs) are key regulatory factors that affect bone metabolism. Prostaglandin E<sub>2</sub> (PGE<sub>2</sub>) regulates bone resorption and bone formation. Prostacyclin (PGI<sub>2</sub>) is one of the major products derived from arachidonic acid by the action of cyclooxygenase and PGI<sub>2</sub> synthase (PGIS). Unlike PGE<sub>2</sub>, there are few reports about the role of PGI<sub>2</sub> in bone regulation. Therefore, we investigated the potential effect of PGI<sub>2</sub> on bone metabolism. We used PGIS knockout (PGIS<sup>-/-</sup>), PGIS heterozygous (PGIS<sup>+/-</sup>), and wild-type mice to investigate the role of PGI<sub>2</sub>. Notably, PGIS <sup>-/-</sup> mice gradually displayed an increase in trabecular bone mass in adolescence. Adult PGIS<sup>-/-</sup> mice showed an increase in trabecular bone volume/tissue volume. Histomorphometric analysis showed that PGIS<sup>-/-</sup> mice displayed increases in both bone formation and bone resorption parameters. Levels of serum osteocalcin and C-telopeptides were increased in adult PGIS<sup>-/-</sup> mice. Furthermore, the increased bone mass patterns were rescued in PGIS<sup>-/tg</sup> mice. In conclusion, adult PGIS<sup>-/-</sup> mice displayed an overall increase in the levels of both bone formation and bone resorption parameters, which suggests that PGI<sub>2</sub> deficiency accelerates high bone turnover activity with a greater increase in bone mass in aging. These results indicated that PGI<sub>2</sub> 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<sub>2</sub> is involved in bone metabolism in vivo.
Date:
2010-02
Relation:
Journal of Endocrinology. 2010 Feb;204(2):125-133.
