Effects Of Zoledronicacid On Proliferation, Differentiation And Mineralization Of Primary Osteoblasts And Fibroblasts

Objective: To investigate effects of zoledronicacid(ZOL) on the proliferation,differentiation and mineralization of primary osteoblasts and fibroblast separated fromclincal Osteogenesis imperfecta(OI) patients and Developmental Dysplasia of the Hip(DDH) victims in vitro.Methods: Primary Osteoblasts(OB) and fibroblasts(FB) isolated from OI and DDHpatients were treated with serial concentrations of ZOL ranging from10-3M to10-13M.Proliferation of primary OB and FB cells were evaluated by MTT essay at the time of2,4,6d. Cell cycle was examed by FACS. ALP activities were assessed by ELISAtest. Mineralization of osteoblasts was measured by the method of alizarin redstain.The expression of genes in osteoblastic mineralization was assayed usingquantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR).Results: MTT essaysed show that high concentration of ZOL may confer toxicity tocultured cells. No obvious inhibitory effect was observed in the concentration of10-7to10-10M. Proliferation was present when the concentration of ZOL was below10-11M(P<0.05). FACS illustrated G1/G0arrest when ZOL concentration in range of10-10Mto10-8M. ZOL did not enhance ALP activity at the concentration of10-8and10-10M.Alizarin red staining illustrated that10-10M concentration of ZOL discouragedmineralization of primary OB. The experimental concentration of ZOL onbone-related osteoblast mRNA expression is inhibition.Conclusion: ZOL’s effect on cell proliferation was dose-dependent and there’s nopromote of bone mineralization when it was not less than10-10M. Meanwhile,differentiation and mineralization may be improved at the low dose ZOL drug.