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Pluripotential Marrow Cells Produce Adipocytes when Transplanted into Steroid-Treated Mice

The effect of steroids on adipogenesis by Dl-BAG, a pluripotent cell cloned from mouse bone marrow and transfected with traceable genes encoding β-galactosidase and neomycin resistance, was investigated in vitro in culture and in vivo after injection into mice. Treatment of Dl-BAG cells in culture with dexamethasone produced an accumulation of lipid vesicles and stimulated expression of the fat cell-specific 422(aP2) mRNA. Fifty-six mice each received 1 × 106 Dl-BAG cells, either by tail-vein injection or by direct injection into the marrow of the right femur. Another 38 mice received either saline injection or no treatment as controls. Half of the animals in each group were treated with 3 mg/kg of methylprednisolone per week. Analysis of marrow blow-outs by flow cytometry, DNA analysis by PCR, and X-gal stain of histological sections indicated that cells transplanted by either intravenous or intramedullary injection had appeared and persisted in the marrow of host mice. Cell sorting by flow cytometry and staining with Sudan IV demonstrated that steroid treatment produced adipogenesis in 5-9% of transplanted cells. The results indicate that steroid-induced differentiation of potentially osteogenic marrow cells into adipocytes in vivo may contribute to the development of osteoporosis and osteonecrosis.