| Project/Area Number |
17590268
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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 |
Pathological medical chemistry
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| Research Institution | Nara Institute of Science and Technology (NAIST) |
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Principal Investigator |
OKA Chio Nara Institute of Science and Technology, Bioscience, assistant Professor, バイオサイエンス研究科, 助手 (30263445)
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| Co-Investigator(Kenkyū-buntansha) |
KAWAICHI Masashi Nara Institute of Science and Technology, Bioscience, Professor, バイオサイエンス研究科, 教授 (00195041)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2006: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | arthritis / HtrA1 / serine protease / hypertrophic chondrocyte / TGF-β / knockout mouse / HtrA1セリンプロテアーゼ / コラーゲン / GFG / collagen / 骨分化 |
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| Research Abstract |
1. HtrA1 expression during normal bone development and in experimental mouse arthritis
HtrA1 was expressed in hypertrophic chondrocytes in the epiphyseal growth plates and articular cartilage of developing mice. In experimental mouse arthritis induced by injection of anti-collagen type II antibodies and LPS, resting chondrocytes in the joints proceed to terminal differentiation and started to express HtrA1. This result shows that hypertrophic change induces HtrA1 expression in chondrocytes both normal and pathological condition.
2. Analysis of HtrA1 KO mice
(1) HtrA1 KO mice showed no remarkable abnormality during development and were born and bred normally. However in more detailed analysis, it was shown that the hypertrophic zones of growth plates were expanded in KO mice. Immunohistochemical analysis with anti-type X collagen and anti-type II collagen indicated that the population of pre-hypertrophic chondrocytes was increased.
(2) In in vitro differentiation system of cartilage, micromass culture, it was shown that the commitment to chondrocytes and the calcification of cartilage nodules prepared from KO mice was normal. However, maturation of cartilage nodules from KO mice occurred more slowly than those from WT mice.
It is known that TGF-β signal inhibits terminal differentiation of chondrocytes. These data indicated that the excessive inhibitory activity by TGF-β suppressed the differentiation of pre-hypertrophic chondrocytes to hypertrophic chondrocytes in HtrA1 KO mice.
(3) HtrA1 KO mice showed resistance to induction of experimental arthritis. The swelling of joints and the destruction of articular cartilage in KO mice was less than those in WT mice.
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