A Study Of The Inhibition Effect Of AZD8835 On Chronic Periodontitis-induced Alveolar Bone Loss

Purpose:To investigate the effects of AZD8835 on osteoclasts and chronic periodontitis by in vitro and in vivo study,aimed at providing evidence for the treatment of periodontitis.Methods: The effect of AZD8835 on cell viability of BMMs cells was studied by CCK-8.The effect of AZD8835 on the formation,differentiation and function of OCs was evaluated by TRAP staining.The effects of AZD8835 on the bone resorption activity of OCs and the expression level of OCs marker genes were evaluated by bone absorption assay and q PCR technique,respectively.The effect of AZD8835 on RANKL-induced osteoclast-relative signaling pathways was detected by Western blot.A model of experimental periodontitis in rats was established.Micro-CT scanning was performed to analyze bone parameters and measurement of the alveolar bone absorption distance of groups.Histochemical staining was used to evaluate the effect of AZD8835 on alveolar bone loss and OCs,respectively.Results: AZD8835 had no cytotoxic effect on BMMs cells at concentrations ?625 n M by CCK-8.TRAP staining revealed that AZD8835 inhibited the formation and differentiation of OCs.Bone absorption experiments suggested that AZD8835 inhibited the bone resorption activity of OCs.q PCR results indicated that AZD8835 inhibited the expression of TRAP,Cts K,Atp6vo0-d2 and CTR genes.Western blot showed that AZD8835 inhibited the phosphorylation of I?B?,AKT and ERK and the activation of NFATc1.The results of animal experiments indicated that the bone volume and trabecular thickness of the AZD8835 treatment group were significantly higher than those of the periodontitis group,and the alveolar bone absorption distance was significantly reduced compared with the periodontitis group.TRAP staining showed that the TRAP-positive cells in the treatment group were significantly reduced compared with the periodontitis group.Conclusion:(1)A ZD8835 inhibited the formation,differentiation and bone resorption activity of OCs,inhibited the phosphorylation of AKT,ERK and I?B?,and inhibited the expression of downstream transcription factor NFATc1 and osteoclast marker genes.(2)AZD8835 inhibited the formation of OCs in rats with periodontitis and reduced alveolar bone loss.