Serum from postmenopausal women directs differentiation of human clonal osteoprogenitor cells from an osteoblastic toward an adipocytic phenotype

A consistent observation in osteoporosis is bone volume reduction accompanied by increased marrow adipose tissue. No single cause linking the two phenomena has yet been identified. In a human progenitor cell clone (hOP 7) derived from bone marrow, however, we have demonstrated that rabbit serum can direct differentiation away from an osteoblast lineage to one of adipocytes. We now report on whether human serum has a similar effect. Serum was collected from 10 pre- and 10 postmenopausal women and from the 10 postmenopausal women before and following 6-week hormone replacement therapy (HRT). hOP 7 cells were cultured with the various sera, and after 7-14 days adipocytogenesis was determined by oil red O staining and lipoprotein lipase (LPL) and glycerol 3-phosphate dehydrogenase (G3PDH) expression. Incubation with 10% premenopausal serum led to labeling of 10.9% of cells (P < 0.05) with oil red O, whereas application of 10% postmenopausal serum led to a much larger effect, 43.5% labeling (P < 0.001 with respect to premenopausal serum). Oil red O positivity was accompanied by loss of type I collagen expression and increased LPL and G3PDH expression. HRT did not reverse the adipocytogenic effect of postmenopausal serum. In conclusion, serum from postmenopausal women contains factors that steer hOP 7 bone progenitor cells toward an adipocytic phenotype, irrespective of HRT. The study suggests a role for serum factors in the development of fatty marrow in postmenopausal osteoporosis.