Title Page
Contents
ABSTRACT 8
Ⅰ. ITRODUCTION 11
Ⅱ. MATERIALS AND METHODS 13
1. Cell culture systemm 13
2. Reagents 13
3. Western blot analysis 14
4. TRAP stain 14
5. Measurement of cytokine production 15
6. Mitochondria / cytosol fractionation 15
7. Actin ring formation assays 15
8. Immunofluorescence microscopy 16
9. RNA-sequencing 17
10. In vivo experiment 17
11. Statistical analysis 18
Ⅲ. RESULTS 19
1. E.coli-induced osteoclast formation is increased in caspase-1/11 KO 19
2. Phosphorylation of IκB and p38 are up-regulated in capase-1/11 KO mice 25
3. GAPDH is highly expressed in caspase-1/11 KO mice 27
4. Mitochondrial fission and mitochondrial ROS are increased in caspase-1/11 KO mice 30
5. LPS-induced bone loss is increased in caspase-1/11 KO mice in vivo 37
6. E.coli-induced osteoclast formation is reduced in Caspase-1 KO mice cells 41
7. E.coli-induced osteoclast formation is decreased in caspase-1 KO mice through IL-1β regulation 45
8. Caspase-1 positively regulates phosphorylation of IκB, p38 and mitochondrial fission 49
9. E.coli-induced osteoclast formation is decreased in GSDMD KO mice 56
10. GSDMD upregulates IL-1β secretion, phosphorylation of IκB, p38 and mitochondrial fission and mitochondrial 60
Ⅳ. CONCLUSION 70
Ⅴ. DISCUSSION 71
Ⅵ. REFERENCES 74
Ⅶ. ABSTRACT IN KOREAN 79