Characterization of progesterone- and dexamethasone- dependent osteoprogenitors in post menopausal women, ovariectomized rats and aging rats

Description

We hypothesized that in humans post-menopausal bone loss as a result of sex steroid deficiency might be related to a decrease in the number of progesterone-dependent osteoprogenitors but not of dexamethasone-dependent osteoprogenitors. This hypothesis was tested in three systems: human bone-derived cell populations from post-menopausal women and bone cell populations derived from ovariectomized rats and aging rats. Our human study showed that dexamethasone-dependent osteoprogenitors can be detected and quantitated in non-transformed human bone cell populations, and that osteoprogenitor proliferation and differentiation can be studied using frozen primary human bone cell populations. However, progesterone-dependent osteoprogenitors could not be detected. A possible explanation for this might be that sex steroid deficiency has caused the disappearance of progesterone-dependent progenitors. We then investigated whether sex steroid deficiency caused by ovariectomy would have different effects on these two classes of osteoprogenitors in rats. We found that ovariectomy of 6 months old rats resulted in a decrease in the number of fibroblastic progenitors and a similar decrease in both dexamethasone- and progesterone-dependent osteoprogenitors. Estrogen enhanced progesterone-dependent bone nodule formation and decreased dexamethasone-dependent bone nodule formation in all populations. We next examined whether the capacity for proliferation and differentiation of progesterone- and dexamethasone-dependent osteoprogenitors in the female rat skeleton changes with age and whether the response to progesterone is related to the levels of progesterone receptors (PR). Our results demonstrated that aging did not affect the number of dexamethasone- and progesterone-dependent osteoprogenitors. With regard to PR, PR-A levels were higher than those of PR-B (≥10-fold) in all cell populations. In cell populations derived from 22.5 to 26 month old rats, the basal levels of PR-A were 5-fold and 2-fold higher, respectively, than those from 3 and 18 month old rats. Interestingly, enhancement of the progesterone effect on PR-A receptor numbers by estrogen was absent in cell populations from 22.5 to 26 month old rats. This corresponded to higher serum estrogen levels in those older rats. We speculate that the high basal levels of PR-A in those cultures (2-4 fold higher than in younger rats) may negatively affect the upregulation of PRs in the whole cell populations.

Subjects

Links

• URL