| Project/Area Number |
19592133
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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 |
Morphological basic dentistry
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| Research Institution | Tokyo Dental College |
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Principal Investigator |
SHIBUKAWA Yoshihiro Tokyo Dental College, 歯学部, 准教授 (50297347)
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| Co-Investigator(Kenkyū-buntansha) |
OTA Mikio 東京歯科大学, 歯学部, 講師 (30322473)
MURAMATSU Takashi 東京歯科大学, 歯学部, 講師 (00276982)
YAMADA Satoru 東京歯科大学, 歯学部, 教授 (20103351)
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| Research Collaborator |
KOYAMA Eiki トーマスジェファーソン大学, 医学部・整形外科学講座 基礎研究部門, 准教授
PACIFICI Maurizio トーマスジェファーソン大学, 医学部・整形外科学講座 基礎研究部門, 教授
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| Project Period (FY) |
2007 – 2009
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| Project Status |
Completed (Fiscal Year 2009)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2008: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 口腔解剖学(含組織学・発生学) / 下顎頭 / 顎関節 / 変形性顎関節症 / 加齢 / 遺伝子発現 / インディアンヘッジホッグ |
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| Research Abstract |
Objectives : Temporomandibular joint (TMJ) osteoarthritis (OA) is mainly caused by aging or occlusal abnormalities such as loss of occlusion. However, the mechanism underlying the early stages of TMJ-OA and its progression remain to be fully clarified. One major problem in OA is the low rate of matrix synthesis and failure of chondrocytes to exceed the rate of matrix degradation. Indian hedgehog (Ihh) is essential for embryonic mandibular condylar growth and disc primordium formation, and its expression is also required for completion of post-natal TMJ growth and organization. In this study, a decrease was observed in expression of collagen II and Aggrecan, the main extra-cellular-matrix (ECM) components of condylar cartilage, in post-natal Ihh-deficient condyles, which is indicative of OA lesions. The purpose of this study was to determine the role of Ihh in the development of TMJ-OA accompanying aging and loss of occlusion in Senescence Accelerated Mouse.
Methods : We used two 4-month
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-old strains : senescence-accelerated prone (SAMP8) mice and senescence-accelerated resistant (SAMR1) mice as a control, each strain comprising 40 males. Each strain was divided into two groups : (1) a milling group (MG : crowns of upper and lower bilateral molars and incisors milled to loss of occlusion and soft dough diet for 4-8 weeks) ; and (2) a non-milling group (NG : no molar or incisor milling and hard pellet diet for 4-8 weeks). The mandibular condyle was evaluated by histology and gene expression by real time polymerase chain reaction.
Results : In the MG, both strains showed a reduction in thickness of the condylar cartilage and gene expression of type II collagen (Col II), Aggrecan and Ihh, and a gradual increase in gene expression of matrix metalloproteinase (MMP)-13 and metalloproteinase with thrombospondin type 1 motif-5 (ADAMTS5) over 4-8 weeks compared to in the NG. Although a significant reduction was observed in gene expression of Col II, Aggrecan and Ihh in the SAMP8 MG compared to in the SAMR1 MG over 4-8 weeks, gene expression of ADAMTS5 and MMP13 showed a significant increase compared to in SAMR1 over 4-8 weeks.
Conclusion : The results suggest that loss of occlusion affects extracellular matrix remodeling, leading to degradation of the mandibular condyle, and that hedgehog signaling affects extracellular matrix remodeling.
The observed degradation of extracellular matrix in SAMP8 indicated development toward more serious TMJ-OA. Less
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