| Project/Area Number |
17592155
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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 |
Orthodontic/Pediatric dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
KURIHARA Saburo Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70126225)
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| Co-Investigator(Kenkyū-buntansha) |
OKAFUJI Norimasa Matsumoto Dental University, Department of dentistry, Associate Professor, 歯学部, 助教授 (50194379)
UEMATSU Setsuo Matsumoto Dental University, Department of dentistry, Lecturer, 歯学部, 講師 (80271378)
TAKAHASHI Naoyuki Matsumoto Dental University, Institute of Oral Science, Professor, 大学院歯学独立研究科, 教授 (90119222)
UDAGAWA Nobuyuki Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (70245801)
NAKAMURA Hiroaki Matsumoto Dental University, Department of dentistry, Professor, 歯学部, 教授 (50227930)
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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: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Osteoclast / Albeolar bone resorption / Human osteoclasts / PGE_2 / EP2 / EP4 / CD14-positive cells / Osteoclast progenitors / BMP / 骨芽細胞 / RANKL / op / opマウス / リゼドロネート / OPG / カルシトニン / ビスフォスホネート |
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| Research Abstract |
We have performed three experiments to elucidate the molecular mechanism by which alveolar bone remodeling induced by orthodontic force. The role of prostaglandin E2 (PGE_2) in osteoclastic bone resorption was carefully examined in this program.
Exp. 1 : PGE_2 synergistically enhances RANKL-induced osteoclastic differentiation of the precursor cells. We investigated the mechanisms of the stimulatory effect of PGE_2 on osteoclast differentiation. The stimulatory effect of PGE_2 on the RANKL-induced osteoclast differentiation of the precursor cells was mediated through EP2 and EP4. TAK1 acted as an adapter molecule linking PKA-induced signals and RANKL-and TNFα-induced such signals in osteoclast precursors. Furthermore, TAK1 is involved in the synergistic effect of cAMP/PKA signals on TNF receptor-and Toll-like receptor 4 (TLR4)-induced signaling pathways. The cAMP/PKA signal may enhance bone resorption induced by RANKL and TNFα through TAK1 in osteoclast precursors.
Exp. 2 : PGE_2 itself
… More
has been shown to directly inhibit bone-resorbing activity of osteoclasts. We explored the mechanism of PGE_2 action in the osteoclastic differentiation of precursor cells. The stimulatory effect of PGE_2 on the RANKL-induced osteoclast differentiation of the precursor cells was mediated through EP2 and EP4. TAK1 acted as an adapter molecule linking PKA-induced signals and RANKL-and TNFα-induced such signals in osteoclast precursors. Furthermore, TAK1 is involved in the synergistic effect of cAMP/PKA signals on TNF receptor-and Toll like receptor 4 (TLR4)-induced signaling pathways. The cAMP/PKA signal may enhance bone resorption induced by RANKL and TNFα through TAK1 in osteoclast precursors.
Exp. 3 : We explored the role of PGE_2 in human osteoclast differentiation in more detail. Unlike mouse macrophage cultures, PGE_2 strongly inhibited RANKL-induced osteoclast formation in human CD14^+ cell cultures. Human osteoclast progenitors produced a soluble unidentified factor(s) in response to PGE_2, which strongly inhibited RANKL-induced osteoclast formation in not only human CD14^+ cell cultures but also mouse macrophage cultures. These results suggest that COX-2 inhibitors may not be suitable therapeutic agents to suppress osteoclastic bone resorption in inflammatory bone diseases. Less
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