Serum-induced adipocytogenesis is not negated by PPARγ blockade

Bone is continuously remodelled during life whereby osteoclastic bone resorption is followed by osteoblastic bone formation. However, in ageing, overall bone mass declines because bone resorption is not matched by new bone formation; and the reduction in bone mass is linked to a concomitant increase in marrow fat. Studies have shown that bone marrow stromal progenitor cells give rise to both osteoblasts and adipocytes, and there is evidence for an inverse relationship between osteoblast and adipocyte formation. Furthermore, we have shown that factors in serum can induce adipocyte differentiation of osteoprogenitor cells. The targeting of the adipocyte/osteoblast differentiation switch may therefore provide a novel therapeutic approach to managing osteopenic disorders. OBJECTIVES: To determine whether blocking PPARγ, the perceived principal adipocytogenic transcription regulator, could negate serum-induced adipocytogenesis of osteoprogenitor cells. METHODS: The human osteosarcoma cell line, SAOS2, capable of adipocytic and/or osteoblastic differentiation, was grown in medium containing either 10% foetal bovine serum (FBS), or 10% rabbit serum (RS - a known inducer of bone marrow cell adipocytogenesis), either with or without T0070907 - a potent and selective antagonist of PPARγ. After 14 days, cells were fixed and stained for lipids with Oil-Red-O, or for calcified nodule formation with alizarin red in replicate plates. RESULTS: There was no significant change in the number of calcified nodules formed by SAOS2 cells due to culturing in different serums, either with or without T0070907. RS induced a significant increase (p<0.05) in adipocytogenesis of SAOS2 cells compared to FBS. There was no significant reduction in the adipocytogenic effect of RS after co-incubation with T0070907. CONCLUSIONS: The adipocytogenic effect of rabbit serum on the human osteosarcoma cell line SAOS2 is not negated by blocking PPARγ with its selective and potent antagonist T0070907.