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

Abstract

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).

Expression profiling of 11β-hydroxysteroid dehydrogenase type-1 and glucocorticoid-target genes in subcutaneous and omental human preadipocytes

“…FABP4, product of the aP2 gene, is regulated by dexamethasone in mouse 3T3L1 cells (Cook et al 1988) as well as in differentiating preadipocytes from rat bone marrow (Atmani et al 2003). This study verified FABP4 gene as a glucocorticoid-target gene but only in SC preadipocytes.…”

Fetal bone cells for tissue engineering

“…This was detected with fetal as well as with adult cells. The combining action of the two hormones was described to strongly increase the adipocyte population and their differentiation but to decrease the osteoblastic cell population in a long-term rat bone marrow culture [55]. Osteoblastic cell proliferation and differentiation were increased by dexamethasone and inhibited by 1a,25-(OH) 2 D 3 .…”

Effects of arachidonic acid and docosahexaenoic acid on differentiation and mineralization of MC3T3‐E1 osteoblast‐like cells

“…Dexamethasone, however, was omitted as it was proven in rat bone marrow stromal cells that dexamethasone per se acts at multiple points in the differentiation process to stimulate osteoblastic maturation. [34][35][36] It has also been suggested that dexamethasone inhibits prostaglandin synthesis. 37 Since PGE 2 is a down-stream product of AA investigated in this study, it was important not to interfere with PGE 2 production.…”