| Project/Area Number |
15390648
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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 |
Periodontal dentistry
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| Research Institution | Aichi-Gakuin University |
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Principal Investigator |
NOGUCHI Toshihide Aichi-Gakuin Univ., Dept.of Periodontology, Sch.of Dent., Professor, 歯学部, 教授 (50014262)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIHARA Yuichi Aichi-Gakuin Univ., Dept.of Periodontology, Sch.of Dent., Professor, 歯学部, 講師 (50261011)
MITANI Akio Aichi-Gakuin Univ., Dept.of Periodontology, Sch.of Dent., Professor, 歯学部, 講師 (50329611)
KOIDE Masanori Aichi-Gakuin Univ., Dept.of Periodontology, Sch.of Dent., Professor, 歯学部, 講師 (10367617)
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| Project Period (FY) |
2003 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,600,000 (Direct Cost: ¥12,600,000)
Fiscal Year 2005: ¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 2004: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | OIP-1 / IFN-γ / Periodontitis / Bone resorption / Osteoclast / IL-1β |
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| Research Abstract |
Periodontitis is a chronic inflammatory disease caused by infections with Gram-negative bacteria and characterized by alveolar bone resorption. It is very critical to inhibit bone resorption for treatment and prevention of periodontitis. The osteoclast (OCL) is the primary bone resorbing cell and there are many reports about intracellular signaling pathway related with OCL differentiation. It is possible to control bone resorption if we could manage this signaling pathway. Our collaborator identified OCL inhibitory peptide-1 (OIP-1/hSca) as a novel inhibitor of OCL formation and bone resorption that is produced by OCLs. OIP-1 is a unique protein from OCLs to be able to inhibit OCL differentiation by itself. Our main object of this study is to seek the possibility for clinical application of OIP-1 in periodontitis by expoloring the mechanism of this OCL inhibition. We used cycle-dependent reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, which demonstrated that interfer
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on-γ (IFN-γ) strongly enhanced OIP-1/hSca mRNA expression in mouse bone marrow cells and osteoblasts. Similarly, interleukin (IL)-12 also enhanced OIP-1 mRNA expression. To determine the participation of OIP-1 in IFN-γ inhibition of OCL formation, we tested the capacity of a neutralizing antibody specific to OIP-1 c-peptide to inhibit IFN-γ's effects on OCL-like cell differentiation of mouse macrophages, RAW 264.7 cells. Anti-OIP-1 c-peptide specific antibody partially neutralized IFN-γ inhibition of OCL differentiation. Furthermore, OIP-1 inhibited phospho-c-Jun (p-c-Jun) kinase activity in RAW 264.7 cells. However, OIP-1/hSca did not affect NF-κB activation hi these cells. Western blot analysis further demonstrated that OIP-1 significantly decreased TNF receptor associated factor 2 (TRAF-2) expression in RAW 264.7 cells. However, OIP-1 had no effect on TRAF-6 expression in these cells. These data show that IFN-γ enhances OIP-1/hSca expression in mouse bone marrow cells and osteoblasts, and that OIP-1 inhibits OCL formation through suppression of TRAF-2 and p-c-Jun kinase activity. These findings suggest the possibility by OIP-1 to inhibit inflammatory bone resorption in periodontitis Less
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