| Project/Area Number |
15592144
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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 |
Surgical dentistry
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
SHUHUA Yang Matsumoto Dental University, School of Dentistry, Research Assistant, 歯学部, 助手 (80360220)
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| Co-Investigator(Kenkyū-buntansha) |
UEMATSU Takashi Matsumoto Dental University, Graduate School of Oral Medicine, Associate Professor, 大学院・歯学独立研究科, 助教授 (40203476)
FURUSAWA Kiyofumi Matsumoto Dental University, Graduate School of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (90165481)
TAKAHASHI Naoyuki Matsumoto Dental University, Graduate School of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (90119222)
UDAGAWA Nobuyuki Matsumoto Dental University, School of Dentistry, Professor, 歯学部, 教授 (70245801)
OZAWA Hidehiro Matsumoto Dental University, Graduate School of Oral Medicine, Professor, 大学院・歯学独立研究科, 教授 (60018413)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2004: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2003: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | periodontal disease / muramyldipeptide / lipopolysaccharide / inflammatory cytokine / Toll-like receptor / bone resorption / osteoblast / osteoclast / ムラミルジペプチド / RANKL / OPG / マクロファージ / インターロイキン1 |
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| Research Abstract |
Muramyl dipeptide (MDP) is the minimal essential structural unit responsible for the immunoadjuvant activity of peptidoglycan. As well as bone-resorbing factors such as 1α,25-dihydroxyvitamin D_3 [1α,25(OH)_2D_3] and PGE_2, lipopolysaccharide (LPS) and IL-1α stimulate osteoclast formation in mouse cocultures of primary osteoblasts and hemopoietic cells. MDP alone could not induce osteoclast formation in the coculture, but enhanced osteoclast formation induced by LPS, IL-1α or TNF-α but not 1α,25(OH)_2D_3 or PGE_2. MDP failed to enhance osteoclast formation from osteoclast progenitors induced by receptor activator of NF-κB ligand (RANKL) or TNF-α. MDP up-regulated RANKL expression in osteoblasts treated with LPS or TNF-α but not 1α,25(OH)_2D_3. Osteoblasts expressed mRNA of Nod2, an intracellular sensor of MDP, in response to LPS, IL-1α or TNF-α but not 1α,25(OH)_2D_3. Induction of Nod2 mRNA expression by LPS but not by TNF-α in osteoblasts was dependent on Toll-like receptor (TLR) 4 and myeloid differentiation factor 88 (MyD88). MDP also enhanced TNF-α-induced osteoclast formation in cocultures prepared from Toll-IL-1 receptor domain-containing adapter protein (TIRAP)-deficient mice through the up-regulation of RANKL mRNA expression in osteoblasts, suggesting that TLR2 is not involved in the MDP-induced osteoclast formation. The depletion of intracellular Nod2 by small interfering RNA blocked MDP-induced up-regulation of RANKL mRNA in osteoblasts. LPS and RANKL stimulated the survival of osteoclasts, and this effect was not enhanced by MDP. These results suggest that MDP synergistically enhances osteoclast formation induced by LPS, IL-1α and TNF-α through RANKL expression in osteoblasts, and that Nod2-mediated signals are involved in the MDP-induced RANKL expression hi osteoblasts.
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