Endocrine Abstracts

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 (VD) 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 in vitro role of ALN on 3T3-L1 adipose differentiation and the potential sinergic role of VD cotreatment.

Procedures: Murine 3T3-L1 and 3T3-F442A preadipocytes were routinely differentiated for 7 days adding ALN and VD 10-9-10-7M, then stained with Red Oil. We analyzed through RT-PCR the effect of such treatments upon mRNA expression of main molecular markers of differentiation, PPARγ and C/EBPα, and VD receptor (VDR).

Results: ALN displayed a marked anti-adipogenic effect on 3T3-L1 cells. VD showed a clear dose-dependent anti-adipogenic effect. Interestingly co-incubation of ALN 10-8M and VD 10-9M did not show synergic effect in inhibition of adipogenesis. PPARγ mRNA expression was significantly reduced by ALN and VD. mRNA expression of C/EBPα was reduced only by the highest doses of VD. Interestingly a concomitant increase in VDR mRNA expression was observed in the presence of ALN and VD, suggesting that VDR may represent the molecular target of the anti-adipogenic effect of ALN.

To confirm this hypothesis, we explored the effects of ALN and VD on 3T3-F44 cells that are in a more advanced differentiation stage in adipogenesis; the results were compared to those obtained in 3T3-L1 cells; we found that expression of VDR mRNA was much lower than in 3T3-L1 cells. Interestingly adipose differentiation in this cell model was not affected by ALN nor VD.

Conclusion: These data represent an indirect evidence of the role of VDR in mediating the anti-adipogenic effect of ALN. Further studies are required to clarify this mechanism.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.