Single Low Dose Bisphosphonate Treatment Enhances Osteogenesis in hMSCs By Exerting Epigenetic Changes

Abstract

Background: Bisphosphonates are analogues of pyrophosphate used to treat bone diseases, like osteoporosis and malignant bone diseases characterized by excessive bone resorption. It has been shown that bisphosphonates hinder bone resorption by interfering with osteoclast activity. Objectives: The present study is planed to investigated the extended effect of a single low dose of bisphosphonate on proliferative, osteogenic behaviour and if treatment with bisphosphonate leads to epigenetic changes in the human mesenchymal stem cells. Methods: We investigated the effects of a single low dose of two BPs [Alendronate (ALE) and Pamidronate (PAM)] on human mesenchymal stem cells (hMSCs) behaviour and phenotype. hMSCs were plated at a density of 5 x 10(5) cells. After 24 hr the medium was changed with growth media containing bisphosphonate at both 100nM and 10nM and were incubated for 24 more h. Cells were then washed, trypsinized and sub-cultured another time with no added exposure to drug. The cell cultures were assayed for proliferation and osteogenic differentiation as well as for changes in DNA methylation. Results: Treating cells with a single low dose of either ALE or PAM (100nM and 10nM) brings about a permanent change in the proliferative and osteogenic behaviour of hMSCs even after passaging the cells. Conclusion: The augmentation of osteogenesis points to the usage of low dose bisphosphonates as an adjunct to implant placement.