2007 Fiscal Year Final Research Report Summary
Analysis of the Nod signals which enhance bone resorption
| Project/Area Number |
17592119
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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 |
YANG Shufa Matsumoto Dental University, Faculty of Dentistry, Research Associate (80360220)
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| Co-Investigator(Kenkyū-buntansha) |
UEMATSU Takashi Matsumoto Dental University, Graduate School for Dentistry, Associate Professor (40203476)
FURUSAWA Kiyofumi Matsumoto Dental University, Graduate School for Dentistry, Professor (90165481)
TAKAHASHI Naoyuki Matsumoto Dental University, Graduate School for Dentistry, Professor (90119222)
UDAGAWA Nobuyuki Matsumoto Dental University, Graduate School for Dentistry, Professor (70245801)
TAKAHASHI Masahiro Matsumoto Dental University, Faculty of Dentistry, Research Associate (90340059)
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| Project Period (FY) |
2005 – 2007
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| Keywords | bone resorption / lipopolysaccharide / peptidoglycan / osteoclasts / RANKL |
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| Research Abstract |
Muramyl dipeptide (MDP) and DAP-containing desmuramyl peptide (iE-DAP) are the minimal essential structural units responsible for the immunoadjuvant activity of peptidoglycan. As well as bone-resorbing factors such as 1α, 25-dihydroxyvitamin D3(1α, 25(OH)2D3) and PGE2, LPS and IL-1 stimulate osteoclast formation in mouse cocultures of primary osteoblasts and hemopoietic cells. MDP or FK156 (artificial compound of iE-DAP) alone could not induce osteoclast formation in the coculture, but enhanced osteoclast formation induced by LPS, IL-1. FK156 enhanced osteoclast formation in the presence of low dose of 1α, 25(OH)2D3 or IL-1. MDP or FK156 failed to enhance osteoclast formation from osteoclast progenitors induced by receptor activator of NF-kB ligand(RANKL). MDP up-regulated RANKL expression in osteoblasts treated with LPS or TNF-α but not 1α, 25(OH)2D3. Osteoblasts expressed mRNA of nucleotide-binding oligomerization domain 2 (Nod2), an intracellular sensor of MDP, in response to LPS, IL-1, or INF-α but not 1α, 25(OH)2D3. 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 or FK156 synergistically enhance osteoclast formation induced by LPS or IL-1through RANKL expression in osteoblasts, and that Nod2-mediated signals are involved in the MDP-induced RANKL expression in osteoblasts as well as Nod1 signaling.
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[Journal Article] Docetaxel inhibits bone resorption through suppression of osteoclast formation and function in different manners.2008
Author(s)
Takahashi M, Takahashi M, Mizoguchi T, Uehara S, Nakamichi Y, Yang S, Naramoto H, Yamashita T, Kobayashi Y, Furusawa K, Yamaoka M, Udagawa N, Uematsu T, Takahashi N
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Journal Title
J Bone Miner Metab (in press)
Description
「研究成果報告書概要(欧文)」より
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