Simvastatin Induces Osteogenic Differentiation and Suppresses Adipogenic Differentiation in Primarily Cultured Human Adipose-Derived Stem Cells

Abstract

-Recent in vitro and in vivo animal studies have reported that statin, a cholesterol-lowering drug, stimulate osteogenic differentiation. In the present study, we investigated the effect of simvastatin on osteogenic and adipogenic differentiation in primarily cultured human adipose-derived stem cells (hADSCs). The simvastatin treatment significantly increased the positive cell numbers in alkaline phosphatase and von Kossa staining, and enhanced the expression levels of bone morphogenic protein (BMP)-2, core binding factor alpha 1 (cbfa1), collgen type I and osteonectin mRNAs. Lastly, hADSCs were cultured in the adipogenic media with or without simvastatin to examine the effect of simvastatin on adipogenic differentiation. In the RT-PCR analysis, there were notable decreases in mRNA expression of aP1, C/EBP-α and PPAR-γ in hADSCs cultivated in simvastatin-added medium, compared to those in simvastatin-free medium. It suggests that the adipogenic differentiation was significantly inhibited by simvastatin treatment. These observations indicate that simvastatin induces osteogenic differentiation and suppresses adipogenic differentiation in hADSCs.

Enhanced Effect of Polyethyleneimine-Modified Graphene Oxide and Simvastatin on Osteogenic Differentiation of Murine Bone Marrow-Derived Mesenchymal Stem Cells

“…Various cell tests were performed in MSCs to evaluate the biological stability and function of the obtained products. According to the literature, Sim showed the best cell proliferation and bone differentiation ability at 1 μM [ 33 , 34 , 35 ]. Thus, in the current study, we developed GS complexes with the concentration of Sim at around 1 μM to evaluate the cellular responses.…”

Simvastatin-Incorporated Drug Delivery Systems for Bone Regeneration

“…The research of Liu et al also has the same result, which shows that simvastatin of 0.01–1 μM can significantly promote the expression of osteogenic genes such as RUNX2 and OCN in hADSCs . Sun et al confirmed that 1 μM simvastatin could induce the expression of BMP-2, core binding factor alpha 1, and type I collagen of hADSCs and inhibit the adipogenic differentiation of hADSCs via down-regulating the expression of adipogenic genes such as PPARγ. Therefore, we conclude that 1 μM may be the optimal concentration for simvastatin to induce osteogenic differentiation of hADSCs.…”

Evaluation of efficacy of simvastatin in bone regeneration following local application in third molar extraction socket: A randomized control trial

“…Statins promote osteoblasts to synthesize BMP2, a growth factor that causes osteoblasts to differentiate, proliferate, mature, and form new bone in vitro and in vivo , as well as inhibits adipocyte differentiation. [ 16 ]…”