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Caprio, M., Antelmi, A., Chetrite, G., Muscat, A., Mammi, C., Marzolla, V., Fabbri, A., Zennaro, M.C. and Feve, B. (2011) Antiadipogenic effects of the mineralocorticoid receptor antagonist drospirenone: Potential implications for the treatment of metabolic syndrome. Endocrinology, 152, 113-125. doi:10.1210/en.2010-0674

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• TITLE: Bisphosphonates and adipogenesis: Evidence for alendronate inhibition of adipocyte differentiation in 3T3-L1 preadipocytes through a vitamin D receptor mediated effect

  AUTHORS: C. Mammi, M. Calanchini, A. Antelmi, A. Feraco, L. Gnessi, S. Falcone, F. Quintarelli, G. M. Rosano, A. Fabbri, M. Caprio

  KEYWORDS: Alendronate; Adipogenesis; Vitamin D; Vitamin D Receptor; 3T3-L1; Mesenchimal Stem Cells

  JOURNAL NAME: Natural Science, Vol.5 No.8, August 9, 2013

  ABSTRACT: Background: Adipocyte and osteoblast derive from the same mesenchimal progenitor. Age-related decrease in bone mass is accompanied by an increase in marrow adipose tissue. Vitamin D3 (VD3) inhibits adipogenesis in 3T3-L1 preadipocytes. Recently it has been demonstrated that alendronate (ALN) inhibits adipogenesis while promoting osteoblast differentiation of mesenchimal stem cells. Aim of the Study: To evaluate the role of ALN on adipocyte differentiation in vitro and the potential synergic role of VD3 co-treatment. Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated in presence of ALN and VD3 10-9 - 10-7 M for 7 days and then stained with Oil Red O. The effect of these treatments on mRNA expression of the main molecular markers of adipocyte differentiation (PPARγ and C/EBPα) and VD Receptor (VDR) were analyzed through RT-PCR. Results: Both ALN and VD3 showed a marked anti-adipogenic effect on 3T3-L1 cells. Co-incubation of ALN 10-8 M and VD3 10-9 M displayed no synergic effect on inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD3. mRNA expression of C/EBPα was reduced only by VD3 treatment. An increase in VDR mRNA expression of 3T3-L1 cells was observed with both ALN and VD3. On the contrary, 3T3-F442A cells, which are in a more advanced adipogenic differentiation stage compared to 3T3-L1, did not express detectable levels of VDR. Interestingly, adipose differentiation of 3T3-F442A was not affected by ALN nor VD3. These results suggest that VDR may represent the molecular target of the anti-adipogenic effect of ALN. Conclusion: VDR plays a critical role in mediating the anti-adipogenic effect of ALN. Further studies to clarify this mechanism are warranted.