Phenotypic effects of continuous or discontinuous treatment with dexamethasone and/or calcitriol on osteoblasts differentiated from rat bone marrow stromal cells.

Osteoblasts are target cells for glucocorticoids and calcitriol, and their phenotype is greatly modified by these hormones. We investigated the effect of continuous or discontinuous hormonal exposure to osteoblasts derived from rat bone marrow stromal cells in long-term subcultures. Stromal cells were grown in primoculture in presence of dexamethasone (dex), but in following subcultures, dex and/or calcitriol were added just after seeding or after a 7-day hormone-free period. Cell proliferation, alkaline phosphatase (ALP) histochemical staining, and enzymatic bioactivity measurement, osteocalcin (OC), ALP and bone sialoprotein (BSP) mRNA expression were used to study the differential effect on osteoblastic phenotype of various conditions of treatment by dex and calcitriol. In primoculture, the osteoblastic differentiation was confirmed by the formation of calcified nodules and by strong expression of ALP, OC, and BSP mRNAs. In subcultures, proliferation of stromal cells was stimulated by dex and inhibited by calcitriol and by both hormones. Cell proliferation was not modified by hormonal lack during 7 days. Continuous hormonal treatment by dex strongly enhanced OC and BSP mRNAs, but apparently did not modified ALP mRNAs expression. Continuous treatment by calcitriol decreased ALP and the dex-induced BSP expression and stimulated the OC mRNAs level, strongly when associated with dex. The population of ALP+ cells and ALP bioactivity were strongly increased by dex, whereas calcitriol or both hormones decreased them. When the subcultures were undergone without hormonal treatment during 7 days, all osteogenic mRNAs strongly decreased even after hormonal recovery. Dex, calcitriol, and both hormones inhibited ALP mRNAs. OC messengers were only weakly detectable with both hormones. ALP+ cell population and ALP bioactivity were decreased after 14 days of hormonal treatment recovery. These results support that continuous presence of glucocorticoids appears as a major key for the permanent expression of the osteoblastic phenotype that is inhibited by calcitriol, in the rat bone marrow.

Atmani H ，Audrain C ，Mercier L ，Chappard D ，Basle MF ... -  《JOURNAL OF CELLULAR BIOCHEMISTRY》

Proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures: effects of dexamethasone and calcitriol.

During bone loss, osteoblast population can be replaced by adipose tissue. This apparent reciprocal relationship between decreased bone density and increased fat formation can be explained by an imbalance in the production of bone-forming and fat-forming cells in the marrow cavity. Thus, osteoblast and adipocyte pathways seem more closely and inversely related. In the present study, we investigated the effects of dexamethasone (dex) and calcitriol [1,25(OH)(2)D(3)] on proliferation and differentiation of osteoblasts and adipocytes in rat bone marrow stromal cell cultures. Stromal cells were grown in primoculture in presence of dex and subcultivated in presence of dex and/or 1,25(OH)(2)D(3). Total cell proliferation, osteoblast and adipocyte-cells number, and -mRNA specific markers were used to study the effects of hormonal treatment on stromal cells. Total cell proliferation was stimulated by dex and inhibited by 1,25(OH)(2)D(3). Dex increased osteoblast and adipocyte cell population whereas calcitriol decreased bone-forming cell number and increased fat cell population. The presence of both hormones led to a strong decrease in osteoblastic cells and to a strong increase in adipocytic cell number. Dex induced mRNA osteoblastic markers expression like bone sialoprotein (BSP) and osteocalcin (OC) and an adipocyte marker expression, the fatty acid binding protein aP2. Calcitriol decreased the dex-induced BSP expression but stimulated slightly OC and aP2 mRNA. The effects of both hormones was to increase strongly OC and aP2 mRNA. These results support that, in rat bone marrow, adipocyte proliferation and differentiation are stimulated by glucocorticoids and calcitriol which act synergically, whereas osteoblastic cell proliferation and differentiation are increased by dex and inhibited by 1,25(OH)(2)D(3).

Atmani H ，Chappard D ，Basle MF 《JOURNAL OF CELLULAR BIOCHEMISTRY》

Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2.

Rickard DJ ，Sullivan TA ，Shenker BJ ，Leboy PS ，Kazhdan I ... -  《DEVELOPMENTAL BIOLOGY》

Dexamethasone induction of osteoblast mRNAs in rat marrow stromal cell cultures.

Leboy PS ，Beresford JN ，Devlin C ，Owen ME ... -  《JOURNAL OF CELLULAR PHYSIOLOGY》

Is 1, 25-dihydroxyvitamin D3 an ideal substitute for dexamethasone for inducing osteogenic differentiation of human adipose tissue-derived stromal cells in vitro?

Zhou YS ，Liu YS ，Tan JG 《CHINESE MEDICAL JOURNAL》