Experimental Repositioning of Geranylgeranylacetone to Enhance Bone Remodeling

抄録

Drug repositioning (DR) is a strategy to explore new medicinal effects from existing approved drugs whose safety and pharmacokinetics have already been established. We focused on geranylgeranylacetone (GGA), which is known as a heat shock proteins (HSPs) inducing agent. GGA is mainly used as a gastric mucosal protective agent; however, its effects on bone tissues have not been studied. Therefore, we hypothesized that “GGA induces HSPs in osteoblasts thereby promotes cell differentiation”, and administered GGA to MC3T3E-1 cells to examine cell responses. Methods: MC3T3E-1 were cultured in osteogenic medium. After the cultures were established, test cultures were exposed to GGA (GGA group). Cell proliferation, collage synthesis and ALP activity were measured on days 7 and 14 of culture. Alizarin Red S staining was performed on days 21 of culture. Results: On days 14 of culture, cell proliferation and collage synthesis were significantly higher in the GGA group than in the control group (P<0.05). On days 7 and 14 of culture, ALP activity was significantly higher in the GGA group than in the Control group (P<0.05). On days 28 of culture, the Alizarin Red S stained areas were significantly higher in the GGA group than in the control group (P<0.05). Conclusion: GGA promoted the differentiation of MC3T3E-1 in an in vitro cell culture model.