The Primary Study Of The Effect Of Zoledronate On Osteoblasts

Bisphosphonates are currently the most important group of antiresorptive agents used in the treatment of metabolic bone ailments, including osteoporosis, Paget's disease, tumor-associated osteolysis and hypercalcemia. Of all kinds of bisphosphonates, zoledronate possesses the most potent anti-resorption property. Despite their wide clinical use and solid effects, the detailed mechanisms of their actions are still not fully understood. It has been accepted that bisphosphonate exerts potent inhibitory effects on osteoclasts both directly and indirectly. While the effects of bisphosphonate on osteoclast have been well-documented, their effects on osteoblast remain controverstial. Bisphosphonate-related osteonecrosis of the jaw is a kind of rare but severe side effect of the drug and brings great physiological and psychological harm to the patients. Therefore,it is necessary for practioners and researcher to pay more attention to the disease. Though several hyposis for the epidology of BRONJ have been proposed, none of them can explain everything perfectly,thus the topic deserves more research efforts.Autophagy is a evolutionary-conservative catabolic process which is critically involved in the clearance of cellular wastes, reconstruction of the cellular structure and the process of growth and development and is closedly related to many individuals' physiological and pathological processes such as aging, immunity system responses, the formation and development of neoplasm as well as neurodegeneration. Unlike the soft tissues which are rich in vessel supply, bone tissue and cartilaginous tissue is characterized by a limited oxygen and blood supply, so it is plausible to regard autophagy in mineralized tissue as a part of the methodology for the osteo/chondrocytes embedded in the mineralized matrix to get their energy supply. Due to the antiangiogenisis ability of the bisphosphate, the hypothesis is proposed that autophagy may play a role in the mechanisms of BRONJ. In the dissertation, the effect of zoledronate on osteoblast proliferation, the expression of the autophagic protein Beclin1 and MAP LC3 in the zoledronate-treated osteoblast and the production of vascular endothelial growth factor(VEGF) by the zoledronate-treated osteoblast are discussed by MTT analysis for the proliferation study, the immunohistochemical staining for the expression study and ELISA for the production of VEGF. And the results proved that zoledronate displayed the inhibitory effect on osteoblast proliferation and the production of VEGF in a dose-dependent manner and all the 3 concentrations of the drug induced the expression of autophagic protein Beclin 1 and MAP LC 3, with 10-8M as the most effective concentration.