Effects of zoledronic acid on osteoblasts in three-dimensional culture
Résumé
Background/purpose: Bisphosphonates (BPs) are synthetic drugs with antitumorand bone antiresorptive activities. The use of BPs is suspected to favor the emergence of osteonecrosisof the jaw (ONJ), a putative side effect whose pathogenesis remains unclear. Thus,we aimed to get insights about the impact of BPs on osteoblasts functions, using a threedimensional(3D) culture model, which is suggested to be more similar to the in vivo tissuesthan monolayers.Materials and methods: Effects of low (0.1 mM) and high (10 mM) concentrations of zoledronicacid were investigated on osteoblasts (hFOB 1.19), cultured as multicellular spheroids (MCS).Proliferation, apoptosis, spheroid growth kinetics, and morphology were studied using the 3-(4,5-dimethyl-thiazoyl-2yl) 2,5-diphenyl-tetrazolium bromide (MTT) and acid phosphatase(APH) assays, caspase 3 Western-blotting, phase contrast imaging and scanning electron microscopy(SEM).Results: Proliferation, apoptosis, and spheroid morphology showed that 10 mM zoledronic acid(ZA) induced a significant reduction in the relative viable cell number, correlated with morphologicalalterations of spheroids, and induction of apoptosis. A lower ZA concentration (0.1 mM)promoted cell proliferation without affecting growth kinetics or spheroid morphology.Conclusion: ZA sensitivity of osteoblasts depends on concentration and experimental models.The dual dose-dependent effects of ZA on osteoblasts cultured as spheroids, thereby promotingor inhibiting cell proliferation, may provide opportunities in tissue engineering. At last, thehFOB spheroid culture system represents a valuable model for the exploration of the molecular
Domaines
Chimie inorganique
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