Metformin alleviates inflammatory bone resorption by modulating apoptosis in osteoblasts
| Autor: | I-Hsuan Su, 蘇懿瑄 |
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| Rok vydání: | 2017 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 105 Inflammatory bone resorption in the periapical lesion causes a hypoxic environment, so the electron transport chain of the mitochondria is blocked and it promotes the production of reactive oxygen species (ROS). Accumulation of ROS not only results in tissue damage, but also leads to osteoblast apoptosis. Metformin is clinically widely used as a hypoglycemic drug, and it also attenuates inflammation, reduced ROS production, affects the function of bone metabolism. In our previous studies, it has been shown that the ROS generated during the inflammatory response is associated with bone loss in the apical region. The larger area of apical lesions, the greater number of apoptotic cells in osteoblasts. However, the detailed mechanism remains to be elucidated. In this study, the human osteosarcoma U2OS cells were incubated in hypoxic environment. MitoSox reagents was used to detect ROS concentration after adding Metformin. To determine whether Metformin affected the hypoxia- induced apoptotic pathway, we detected the protein expression of cytochrome C, apoprotein caspase-9 and poly (adenosine phosphate ribose) polymerase (PARP) fragments in the pathway by Western blott. Further more, the rat model with induced apical lesion were also designed. Metformin treatment was performed after standard root canal debridement, and the healing of the apical lesion was investigated by imaging analysis and tissue immunostaining. The results showed that hypoxia stimulation increased the concentration of ROS in the mitochondria, the release of cytochrome C and increase the expression of caspase-9 and PARP cleavage, indicating hypoxia induced apoptosis in U2OS. However, adding Metformin under the same conditions not only reduce the concentration of ROS in the mitochondria, but also inhibited the release of cytochrome C and enhance the expression of caspase-9 and PARP cleavage. In the animal experiments, a number of cells apoptosis were observed in the apical inflammatory tissue. However, Metformin effectively reduced the area of apical lesion by local administration in the root canal. In conclusion, we found that osteoblast apoptosis induced by functionally-altered mitochondria in hypoxia can be suppressed by Metformin through inhibiting production of ROS. We also found that local administration of Metformin attenuated inflammatory bone resorption in rat apical lesions. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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