Inhibition of Adipogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells by a Phytoestrogen Diarylheptanoid from Curcuma comosa

We investigated the effect of a phytoestrogen, (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (DPHD), from Curcuma comosa Roxb. (Zingiberaceae family) on the adipogenic differentiation of mesenchymal progenitors, human bone marrow-derived mesenchymal stem cells (hBMSCs). DPHD inhibited adipocyte differentiation of hBMSCs by suppressing the expression of genes involved in adipogenesis. DPHD at concentrations of 0.1, 1, and 10 mu M significantly decreased triglyceride accumulation in hBMSCs to 7.1 +/- 0.2, 6.3 +/- 0.4, and 4.9 +/- 0.2 mg/dL, respectively, compared to the nontreated control (10.1 +/- 0.9 mg/dL) (p < 0.01). Based on gene expression profiling, DPHD increased the expression of several genes involved in the Wnt/beta-catenin signaling pathway, a negative regulator of adipocyte differentiation in hBMSCs. DPHD also increased the levels of essential signaling proteins which are extracellular signal-regulated kinases 1 and 2 (ERK1/2) and glycogen synthase kinase 3 beta (GSK-3 beta) that link estrogen receptor (ER) signaling to Wnt/beta-catenin signaling. In conclusion, DPHD exhibited the anti-adipogenic effect in hBMSCs by suppression of adipogenic markers in hBMSCs through the activation of ER and Wnt/beta catenin signaling pathways. This finding suggests the potential role of DPHD in preventing bone marrow adiposity which is one of the major factors that exacerbates osteoporosis in postmenopause.