Involvement of Cot/Tp12 in bone loss during periodontitis.
Periodontitis causes resorption of alveolar bone, in which RANKL induces osteoclastogenesis. The binding of lipopolysaccharide to Toll-like receptors causes phosphorylation of Cot/Tp12 to activate the MAPK cascade. Previous in vitro studies showed that Cot/Tp12 was essential for the induction of RANKL expression by lipopolysaccharide. In this study, we examined whether Cot/Tp12 deficiency reduced the progression of alveolar bone loss and osteoclastogenesis during experimental periodontitis. We found that the extent of alveolar bone loss and osteoclastogenesis induced by ligature-induced periodontitis was decreased in Cot/Tp12-deficient mice. In addition, reduction of RANKL expression was observed in periodontal tissues of Cot/Tp12-deficient mice with experimental periodontitis. Furthermore, we found that Cot/Tp12 was involved in the induction of TNF-alpha mRNA expression in gingiva of mice with experimental periodontitis. Our observations suggested that Cot/Tp12 is essential for the progression of alveolar bone loss and osteoclastogenesis in periodontal tissue during experimental periodontitis mediated through increased RANKL expression.
Ohnishi
T
T
Department of Developmental Medicine, Kagoshima University, Sakuragaoka, Japan.
Okamoto
A
A
Kakimoto
K
K
Bandow
K
K
Chiba
N
N
Matsuguchi
T
T
D016301:Alveolar Bone Loss / Q000097:blood / Q000378:metabolism*; D000818:Animals; D002454:Cell Differentiation; D051546:Cyclooxygenase 2 / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D008070:Lipopolysaccharides; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism; D010513:Periodontal Ligament / Q000166:cytology / Q000378:metabolism; D010518:Periodontitis / Q000097:blood / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D053245:RANK Ligand / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000097:blood
D016207:Cytokines; D008070:Lipopolysaccharides; D011518:Proto-Oncogene Proteins; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D051546:Cyclooxygenase 2; D020930:MAP Kinase Kinase Kinases; C489843:Map3k8 protein, mouse; D020929:Mitogen-Activated Protein Kinase Kinases