DEXAMETHASONE PROMOTES EXPRESSION OF MEMBRANE-BOUND MACROPHAGE-COLONY-STIMULATING FACTOR IN MURINE OSTEOBLAST-LIKE CELLS

The mechanisms by which glucocorticosteroids promote osteoclastogenesi s in vitro are uncertain. As macrophage colony-stimulating factor (MCS F) is critical for osteoclastogenesis, we hypothesized that glucocorti costeroids might regulate membrane-bound MCSF (mMCSF) and soluble MCSF (sMCSF) production by stromal cells or osteoblasts. ST2 cells or muri ne calvarial osteoblasts (MOBs) were treated with dexamethasone (Dex; 100 mM) and/or 1,25-dihydroxyvitamin D [1,25(OH)(2)D; 10 nM] for 3 day s. Control values for mMCSF and sMCSF as units per 100,000 cells were 9 +/- 1.4 and 511 +/- 56 in ST2 cells and 5.9 +/- 0.8 and 379 +/- 47 i n MOB cells, respectively. Dex increased mMCSF to 156 +/- 16% and 143 +/- 26% compared with the control value in ST2 and MOB cells, respecti vely, whereas 1,25-(OH)(2)D caused increases of 195 +/- 16% and 164 +/ - 21%. In the presence of both Dex and 1,25-(OH)(2)D, mMCSF increased to 209 +/- 24% and 216 +/- 26% in the two cell types, respectively. 1, 25-(OH)(2)D caused modest increases in sMCSF, as expected, in both cel l types (153 +/- 6% and 122 +/- 4%). Dex inhibited 1,25-(OH)(2)D-stimu lated sMCSF (115 +/- 7% of control) in ST2 cells. Analysis of mMCSF tr anscript levels by semiquantitative RT-PCR revealed Dex-stimulated inc reases of 170 +/- 11% in ST2 cells and 126 +/- 16% in MOB cells compar ed with the control level. The increased expression of the transcript for sMCSF in the presence of Dex and 1,25-(OH)(2)D, measured by both R T-PCR and Northern analysis (219 +/- 53% and 242%, respectively), desp ite inhibition of sMCSF protein, indicated that the inhibitory effect of Dex in ST2 cells was posttranscriptional. Half-life studies showed that Dex prolonged MCSF messenger RNA from 2.8 to 7.5 h. These results suggest that Dex influences osteoclastogenesis by increasing the expr ession of mMCSF by accessory cells in culture.