title: The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells.
abstract: The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This in vitro study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This in vitro study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).
authors: Molecular Basis of Disease Group, Regenerative Medicine Centre, Menzies Health Institute, QLD, School of Dentistry and Oral Health, Griffith University, Gold Coast Campus, Australia.
authors: Dileep
authors: D
authors: Sharma
authors: Molecular Basis of Disease Group, Regenerative Medicine Centre, Menzies Health Institute, QLD, School of Dentistry and Oral Health, Griffith University, Gold Coast Campus, Australia.
authors: Stephen Mark
authors: SM
authors: Hamlet
authors: Molecular Basis of Disease Group, Regenerative Medicine Centre, Menzies Health Institute, QLD, School of Medicine, Griffith University, Gold Coast Campus, Australia.
authors: Eugen Bogdan
authors: EB
authors: Petcu
authors: Molecular Basis of Disease Group, Regenerative Medicine Centre, Menzies Health Institute, QLD, School of Dentistry and Oral Health, Griffith University, Gold Coast Campus, Australia.
authors: Saso
authors: S
authors: Ivanovski
mesh_terms: D000943:Antigens, Differentiation / Q000096:biosynthesis*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D004164:Diphosphonates