Prostaglandins (PGs) are key regulatory factors that affect bone metabolism. Prostaglandin E2 (PGE2) regulates bone resorption and bone formation. Prostacyclin (PGI2) is one of the major products derived from arachidonic acid by the action of cyclooxygenase and PGI2 synthase (PGIS). Unlike PGE2, there are few reports about the role of PGI2 in bone regulation. Therefore, we investigated the potential effect of PGI2 on bone metabolism. We used PGIS knockout (PGIS−/−), PGIS heterozygous (PGIS+ /−), and wild-type mice to investigate the role of PGI2. 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 PGI2 deficiency accelerates high bone turnover activity with a greater increase in bone mass in aging. These results indicated that PGI2 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 PGI2 is involved in bone metabolism in vivo.
Chalida Nakalekha, Chieko Yokoyama, Hiroyuki Miura, Neil Alles, Kazuhiro Aoki, Keiichi Ohya and Ikuo Morita
Koichiro Taguchi, Kazuo Kajita, Yoshihiko Kitada, Masayuki Fuwa, Motochika Asano, Takahide Ikeda, Toshiko Kajita, Tatsuo Ishizuka, Itaru Kojima and Hiroyuki Morita
Despite extensive investigation, the mechanisms underlying adipogenesis are not fully understood. We previously identified proliferative cells in adipose tissue expressing adipocyte- specific genes, which were named small proliferative adipocytes (SPA). In this study, we investigated the characteristics and roles of SPA in adipose tissue. Epididymal and inguinal fat was digested by collagenase, and then SPA were separated by centrifugation from stromal vascular cells (SVC) and mature white adipocytes. To clarify the feature of gene expression in SPA, microarray and real-time PCR were performed. The expression of adipocyte-specific genes and several neuronal genes was increased in the order of SVC < SPA < mature white adipocytes. In addition, proliferin was detected only in SPA. SPA differentiated more effectively into lipid-laden cells than SVC. Moreover, differentiated SPA expressed uncoupling protein 1 and mitochondria-related genes more than differentiated SVC. Treatment of SPA with pioglitazone and CL316243, a specific β3-adrenergic receptor agonist, differentiated SPA into beige-like cells. Therefore, SPA are able to differentiate into beige cells. SPA isolated from epididymal fat (epididymal SPA), but not SPA from inguinal fat (inguinal SPA), expressed a marker of visceral adipocyte precursor, WT1. However, no significant differences were detected in the expression levels of adipocyte-specific genes or neuronal genes between epididymal and inguinal SPA. The ability to differentiate into lipid-laden cells in epididymal SPA was a little superior to that in inguinal SPA, whereas the ability to differentiate into beige-like cells was greater in inguinal SPA than epididymal SPA. In conclusion, SPA may be progenitors of beige cells.