2005 Fiscal Year Final Research Report Summary
Study on the molecular mechanism of alveolus bone resorption induced periodontal diseases
| Project/Area Number |
16390535
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional basic dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
TAKAHASHI Naoyuki Matsumoto Dental University Graduate School of Oral Medicine, Department of Hard Tissue Research, Professor, 大学院・歯学独立研究科, 教授 (90119222)
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| Co-Investigator(Kenkyū-buntansha) |
OZAWA Hidehiro Graduate School of Oral Medicine, Department of Hard Tissue Research, Professor, 大学院・歯学独立研究科, 教授 (60018413)
KAWAKAMI Toshiyuki Graduate School of Oral Medicine, Department of Hard Tissue Research, Professor, 大学院・歯学独立研究科, 教授 (80104892)
MIYAZAWA Toshio Graduate School of Oral Medicine, Department of Hard Tissue Research, Professor, 大学院・歯学独立研究科, 教授 (90147637)
NAMKAMURA Midori School of Dentistry, Department of Biochemistry, assistant Professor, 歯学部, 講師 (90278177)
NINOMIYA Tadashi Institute for Oral Science, Hard Tissue Research, Research Associate, 総合歯科医学研究所, 助手 (00360222)
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| Project Period (FY) |
2004 – 2005
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| Keywords | osteoclast / osteoblast / inflammatory bone resorption / Lipopolysaccharide / Muramyl dipeptide / MyD88 / Prostaglandin E_2 / Bone morphogenetic protein |
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| Research Abstract |
The research projects "Identification of the TRAF6 interacting molecules by using the two-hybrid system", "Establishments of animal models for periodontal diseases", and "Development of the treatment method for periodontal diseases using the animal models" are currently performed in our laboratory. The results of the other projects were as follows.
1.Using MyD88 deficient mice and TRIF deficient mice, the RANKL expression induced by LPS and IL-1 in osteoblasts required only the MyD88 signals but not TRIF signals
2.Nod2 is s involved in RANKL expression in osteoblasts induced by muramyl dipeptide (MDP), a component of peptidoglycan, as an intracellular receptor for MDP.
3.PGE_2 directly acts on murine osteoclast progenitors and enhances their differentiation into osteoclasts induced by RANKL. On the other hand, when EP4 was transduced into osteoclasts, like calcitonin, PGE_2 inhibited pit-forming activity of osteoclasts through cAMP-PKA signals.
4.In vitro culture systems for human osteoclast formation was established, and effects of calcitonin on human osteoclasts were examined. Both PKA- and PKC-mediated signals were required for the calcitonin-induced human osteoclast function. In addition, PGE_2 strongly inhibits the differentiation of human osteoclast progenitors into osteoclasts. PGE_2 stimulates the production of an inhibitory factor(s) by human osteoclast progenitors, and inhibits their differentiation into osteoclasts.
5.Using OPG deficient mice and RANKL deficient mice, we examined osteoclast formation in ectopic bone induced by bone morphogenetic protein 2 (BMP-2). It was shown that osteoblasts provide the critical microenvironment for the action of RANKL.
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