https://scholars.lib.ntu.edu.tw/handle/123456789/458885
標題: | Simvastatin alleviates bone resorption in apical periodontitis possibly by inhibition of mitophagy-related osteoblast apoptosis | 作者: | Yang C.-N. SANG-HENG KOK HAN-WEI WANG JENNY ZWEI-CHIENG CHANG EDDIE HSIANG HUA LAI CHIA-TUNG SHUN Yang H. Chen M.-H. Hong C.-Y. SZE-KWAN LIN |
公開日期: | 2019 | 卷: | 52 | 期: | 5 | 起(迄)頁: | 676-688 | 來源出版物: | International Endodontic Journal | 摘要: | Aim: To assess the connection between mitophagy and hypoxia-induced apoptosis in osteoblasts and whether simvastatin alleviates bone resorption in apical periodontitis through modulation of mitophagy-related apoptosis. Methodology: Hypoxia-induced generation of reactive oxygen species in mitochondria and changes in mitochondrial membrane potential were evaluated, respectively, by MitoSOX and JC-1 fluorescence dye signalling. Accumulation of mitophagy markers PTEN-induced putative kinase 1 (PINK1) and Parkin in mitochondria was examined by Western blotting and immunofluorescence microscopy. Osteoblast apoptosis was assessed by Western analysis of cleaved-poly (adenosine diphosphate ribose) polymerase (PARP). In a rat model of induced apical periodontitis, the therapeutic effect of simvastatin and its action on osteoblast mitophagy and apoptosis were examined. anova, Fisher's and Student's t-test were used for data analysis. Results: Hypoxia-induced mitochondrial dysfunction and stimulated mitophagy in osteoblasts. Hypoxia also provoked apoptosis in osteoblasts and inhibition of mitophagy decreased hypoxia-augmented apoptotic activity. Simvastatin alleviated hypoxia-induced mitochondrial dysfunction, mitophagy and apoptosis. The protective action of simvastatin against apoptosis was related to its antimitophagy activity. Experiments in the rat model of induced apical periodontitis supported the laboratory findings. Simvastatin treatment mitigated periapical bone loss and reduced the activities of apoptosis and mitophagy in regional osteoblasts. Conclusions: The results suggest that modulation of osteoblast mitophagy may help diminish bone loss associated with inflammation and has potential as an auxiliary therapy for apical periodontitis. ? 2018 International Endodontic Journal. Published by John Wiley & Sons Ltd |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/458885 | DOI: | 10.1111/iej.13055 | SDG/關鍵字: | simvastatin; animal; apoptosis; human; mitophagy; osteoblast; osteolysis; rat; tooth periapical disease; Animals; Apoptosis; Bone Resorption; Humans; Mitochondrial Degradation; Osteoblasts; Periapical Periodontitis; Rats; Simvastatin |
顯示於: | 牙醫學系 |
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