STEROID-INDUCED ADIPOGENESIS IN A PLURIPOTENTIAL CELL-LINE FROM BONE-MARROW

We studied the effect of steroids on the differentiation of a pluripot ential mesenchymal cell with use of a cell line (D1) from mouse bone-m arrow stroma, The cells were treated with Increasing (10(-9), 10(-8), and 10(-7)-molar) concentrations of dexamethasone for increasing durat ions ranging from forty-eight hours to twenty-one days. The appearance of triglyceride vesicles in the cells indicated that this treatment h ad induced the differentiation of the cell into adipocytes. The number of cells that contained the triglyceride vesicles and the expression of a fat-cell-specific gene, 422(aP2), increased with longer durations of exposure to dexamethasone and with higher concentrations of the st eroid, Treatment with dexamethasone also diminished the expression of alpha 1 type-I collagen mRNA and osteocalcin mRNA. The data indicate t hat dexamethasone stimulates the differentiation of cells in bone-marr ow stroma into adipocytes as well as the accumulation of fat in the ma rrow at the expense of expression of type-I collagen and osteocalcin m RNA, thereby suppressing differentiation into osteoblasts. CLINICAL RE LEVANCE: Steroid-induced adipogenesis by bone progenitor cells in marr ow may influence the development of osteonecrosis, it is therefore imp ortant to consider the investigation of a treatment, such as the inhib ition of the metabolism and accumulation of fat in marrow, that can pr event the onset of osteonecrosis.