THE EFFECTS OF DEXAMETHASONE AND 1,25-DIHYDROXYVITAMIN D-3 ON OSTEOGENIC DIFFERENTIATION OF HUMAN MARROW STROMAL CELLS IN-VITRO

Effects of dexamethasone and 1,25-dihydroxyvitamin D, [1,25(OH)(2)D-3] were studied in cultures of adult human marrow stromal cells. In primary culture: dexamethasone (10(-8) M) increased the number of fibroblast colonies formed but decreased their average size. The number of colonies expressing alkaline phosphatase activity was increased, consistent with the enhancement of osteogenic differentiation by this glucocorticoid. In secondary culture, osteogenic differentiation was assessed by measurement of the steady-state levels of particular mRNAs that are characteristic of cells of the osteoblast lineage. The mRNAs for alpha(1)(I)-procollagen, alkaline phosphatase, osteopontin and bone sialoprotein were expressed under all culture conditions used. In contrast, osteocalcin mRNA expression was detectable only in cultures treated with 1,25(OH)(2)D-3 (10(-8) M). Addition of 1,25(OH)(2)D-3 to control cultures increased the expression of the mRNAs for alkaline phosphatase and osteopontin but had no significant effect on bone sialoprotein expression. The highest levels of expression of the mRNAs for alkaline phosphatase, bone sialoprotein and osteocalcin were observed in dexamethasone-treated cultures to which 1,25(OH)(2)D-3 had been added. These results demonstrate that, as earlier found in other species, dexamethasone and 1,25(OH)(2)D-3 promote the osteogenic differentiation of human marrow stromal cells as measured by expression of these osteogenic markers.