| Project/Area Number |
17591955
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
YAMASHITA Teruhito Matsumoto Dental University, Institute for Oral Science, Assistant Professor, 総合歯科医学研究所, 講師 (90302893)
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| Co-Investigator(Kenkyū-buntansha) |
UDAGAWA Nobuyuki Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70245801)
NINOMIYA Tadashi Matsumoto Dental University, Institute for Oral Science, Research Associate, 総合歯科医学研究所, 助手 (00360222)
NAKAMICHI Yuko Matsumoto Dental University, Institute for Oral Science, Research Associate, 総合歯科医学研究所, 助手 (20350829)
MIZOGUCHI Toshihide Matsumoto Dental University, Institute for Oral Science, Assistant Professor, 総合歯科医学研究所, 講師 (90329475)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | osteoclasts / MAP kinase / bone resorption / survival / Yeast Two Hybrid Screening / p38 MAPキナーゼ / MKK6 / アデノウイルスベクター |
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| Research Abstract |
Osteoclasts are derived from the monocyte/macrophage lineage and are responsible for bone resorption. p38 MAPK was essential for osteoclast differentiation but the survival and activation of osteoclasts were not affected by SB203580, a specific inhibitor for p38MAPK. Bone resorption factors such as IL-1 and lipopolysaccharide (LPS) activate MAPK signaling. To clarify the role of p38MAPK in osteoclast function, we measured the phosphorylated status of MAPKs and examined whether force-phosphorylation of p38MAPK modulates osteoclast function. Although osteoclasts expressed p38 MAPK at the level equivalent to that of bone marrow macrophages, phosphorylation of p38 MAPK was not induced by LPS in osteoclasts. MKK3 and MKK6, upstream kinases for p38 MAPK, were expressed in osteoclasts. Phosphorylation of MKK3/6 was not increased by IL-1 or LPS, even JNK and ERK were activated. Adenoviral expression of a constitutively active form of MKK6 (MKK6CA) in osteoclasts resulted in phosphorylation of p38 MAPK. The survival activity of MKK6CA-expressing osteoclasts evaluated at 48h was as high as that of IL-1-treated cells. Moreover, the number of survived osteoclasts which expressed MKK6CA decreased to a one third by SB203580. Neither bone resorbing activity on dentin slices nor the expression levels of cathepsin K were different between MKK6CA-expressing osteoclasts and control. These findings suggest that osteoclasts keep own p38 MAPK signaling in an inactive state to abort their survival. In a pathological state, p38 MAPK is activated in osteoclasts and it might extend osteoclast lifespan.
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