Effects of alendronate on adipogenic differentiation of bone marrow stromal cells derived from ovariectomized rats

Abstract

Objective To explore the effects of alendronate on adipogenic differentiation of bone marrow stremal cells (BMSCs) and the role of mitogen-activated protein kinases (MAPK) signal pathway in this process. Methods BMSCs were derived from 9-month-old ovariectomized SD rats and exposed to 0.01, 0.1, 1, 10 μmol/L of alendronate for 2 weeks. The number of BMSCs was counted under light microscope after oil red O staining. The expression of peroxisome proliferators activated receptor-γ, 2 (PPAR-γ2) was measured by RT-PCR. The effect of alendronate on MAPK signal pathway was detected by Western blot. Results After two weeks of induction of BMSCs by alendronate, BMSCs with positive oil red O staining significantly decreased as the increase of the concentration of alendronate (P <0.01), so did the expression of PPAR-γ2. The expression level of PPAR 2 increased when exposing BMSCs to ERK1/2 or JNK specific inhibitors, PD98059 and SP600125 for two weeks. However, the expression level of PPAR 2 decreased when exposing BMSCs to SB203580 (an inhibitor of p38) for two weeks. Condusion Alendronate can inhibit adipogenic differentiation of BMSCs derived from ovariectomized rats in a doso-dependent manner by activating ERK1/2 and JNK rather than p38. Key words: Alendronate; Bone marrow stromal cells; Mitogen-activated protein kinases; Osteoporosis