Influence of geranylgeraniol on cell viability, migration ability and apoptosis rate of endothelial progenitor cells (EPC) after bisphosphonate treatment in vitro

Introduction: Aim of this study is to analyze the influence of geranylgeraniol (GG) on cell viability, migration ability and apoptosis rate of endothelial progenitor cells (EPC) after bisphosphonate treatment in vitro. Material and Methods: EPCs were isolated from human peripheral blood and cultured. The cells were incubated with different non nitrogen- and nitrogen-containing bisphosphonates (clodronate, ibandronate, pamidronate, zoledronate; 0, 5, 50 µM) and substituted with GG (10 µM). A second experimental series without GG served as controls. After 72 h, cell viability was analyzed by a MTT- and Presto Blue-assay. Migration ability was detected by a migration-assay and apoptosis rate of the EPCs was analyzed by a Tunel- and a Toxi Light-assay. Results: Negative effects of the nitrogen-containing bisphosphonates on EPCs could be shown in the test lines without GG in all assays. In the GG test lines, EPC demonstrated a significantly increased cell viability (MTT/PrestoBlue: p each 0.05) and migration ability (Scratch wound/migration: p each 0.05). Concerning the apoptosis rates, a decreased number of apoptotic cells in the Tunel-assay (p each 0.05) and a decreased adenylate kinase release in the ToxiLight-assay (p each 0.05) could be observed. Concerning the non nitrogen-containing clodronate, whether in the test line without GG nor in the test line with GG significant differences could be demonstrated in any assay (p each >0.05). Discussion: GG substitution rescued the negative effects of bisphosphonates on EPCs significantly. GG might improve the reduced angiogenesis after bisphophonate treatment in vivo and therefore improve the wound healing in the affected patients. Keywords: bisphosphonate, geranylgeraniol, cell viability, EPC