Prostaglandins are candidates for post-menopausal serum-induced adipocytogenesis of osteoprogenitor cells

Porosity of mandibular bone, both cortical and alveolar, increases markedly following the menopause. Oestrogen deficiency after menopause is associated with accelerated bone loss, whereby bone resorption exceeds new bone formation during each bone remodelling cycle. A deficit in osteoblast differentiation might contribute to this post-menopausal bone loss, since incubation of osteoprogenitor cells with serum from post-menopausal women induces their differentiation to adipocytes rather than osteoblasts. Furthermore, we recently reported that oestrogen hormone replacement therapy (HRT) did not offset the adipogenic affect of post-menopausal serum on bone progenitor cells. The nuclear receptor PPARγ is considered the dominant regulator of adipogenesis and therefore the likely principle controlling adipocyte differentiation. OBJECTIVES: To determine whether natural ligands of PPARγ, which reside in human serum, could induce the adipocytogenesis of human osteoprogenitor cells. METHODS: The human osteoprogenitor cell line, hOP 7, was incubated with 10% foetal bovine serum (FBS), 10% rabbit serum (a known inducer of bone marrow cell adipocytogenesis), 10% post- menopausal human serum, or with 10% FBS plus PPARγ natural ligands and associated precursors and metabolites: 15-deoxy12,14prostaglandinJ2, prostaglandinJ2, or prostaglandinD2. The cells were fixed after 7 days incubation and stained for lipids with Oil-Red-O. mRNA analyses were performed to determine the expression of adipocyte markers lipoprotein lipase (LPL) and glycerol phosphate 3-dehydrogenase (GPD). RESULTS: Rabbit serum (p<0.001) and post-menopausal human serum (p<0.01) induced adipocytogenesis of hOP-7 cells as determined by increased Oil Red O cell staining, and LPL and GDP expression. A highly significant increase in adipocytogenesis was seen in hOP-7 cells incubated with 15-deoxy12,14prostaglandinJ2 (p<0.01), prostaglandinJ2 (p<0.001), or prostaglandinD2 (p<0.001). CONCLUSIONS: PPARγ natural ligands and associated precursors and metabolites, which reside within human serum, are likely candidates for the serum-induced adipocytogenic effect on hOP 7 cells.