Study on HtrA Serine Protea we Family Proteins Which Inhibit Signaling of TGF-βs
| Project/Area Number |
17390079
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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 |
General medical chemistry
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| Research Institution | Nara Institute of Science and Technology |
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Principal Investigator |
KAWAICHI Masashi Nara Institute of Science and Technology, School of Biological Sciences, Professor (00195041)
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| Co-Investigator(Kenkyū-buntansha) |
OKA Chio Nara Institute of Science and Technology, School of Biological Sciences, Assistant Professor (30263445)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥13,440,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥840,000)
Fiscal Year 2007: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2006: ¥5,300,000 (Direct Cost: ¥5,300,000)
Fiscal Year 2005: ¥4,500,000 (Direct Cost: ¥4,500,000)
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| Keywords | HtrA1 / Osteoarthritis / Collagens / C-pronentide / Bone density / Osteocalcine / Calcification / Hypertrophic chondrocvte / HtrA1 / HtrAセリンプロテアーゼ / 関節炎 / 加齢黄斑変性症 / bFGF / 遺伝子破壊マウス / 軟骨分化 / 骨芽細胞分化 / 細胞外基質 / プロテオグリカン / TGF-β / 肥大軟骨 / 骨芽細胞 / コラーゲン |
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| Research Abstract |
1. Expression patterns of mouse HtrA1 after birth are analyzed with focus on the skeletal tissues. HtrA1 is expressed in cartilage by a subgroup of hypertrophic chondrocytes which undergo cartilage matrix calcification and cell death. In bone, HtrA1 is expressed by flat osteoblasts and osteocytes entrapped in the bone.
2. Upon induction of experimental rheumatoid arthritis in mouse, HtrA1 content in the joint cartilage is increased several-fold. Hypertrophic chondrocytse which are rarely seen in normal joint cartilage appear in the cartilage in a large number and produce HtrA1. The expression of HtrA1 in the arthritic cartilage, therefore, recapitulates normal development of cartilage.
3. HtrA1 knock-out mice are produced. The mice grow and reproduce normally. Their skeletal tissues are free from abnormities and osteogenesis proceeds normally. However, there is increase in number of hypertrophic chondrocyte which produce osteocalcine and type X collagen around the secondary ossification center in the day 9 tibia, suggesting some disturbance in chondrogenesis.
4. The KO mice respond to the induction of arthritis normally.
5. ES cells with disruption in HtrA3 gene are isolated to produce HtrA3 KO mice.
6. Production of full-length HtrA1 protein in a large amount is tried in CHO cells without success. Pichia yeast cell are now being tried.
7. HtrA1 is found to be able to partially degrade monomeric type I collagen in the excretion pathway.
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Report
(4 results)
Research Products
(7 results)
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[Journal Article] Expression of mouse HtrAl serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis2005
Author(s)
Tsuchiya, A., Yano, M., Tocharus, J., Kojima, H., Fukumoto, M., Kawaichi, M. and Oka, C.
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Journal Title
Description
「研究成果報告書概要(和文)」より
Related Report
Peer Reviewed
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[Journal Article] Expression of mouse HtrA1 serine protease in normal bone and cartilage and its upregulation in joint cartilage damaged by experimental arthritis2005
Author(s)
Tsuchiya, A., Yano, M., Tocharus, J., Kojima, H., Fukumoto, M., Kawaichi, M., Oka, C
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Journal Title
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Presentation] Mammalian HtrA1 is a highly regulated serine protease2006
Author(s)
Chio, Oka, Murwantoko, Masato, Yano, Yoshifumi, Ueta, Hisae, Kojima, Akiho, Tsuchiya, Masashi, Kawaichi
Organizer
20th IUBMB International Congress
Place of Presentation
Kyoto
Description
「研究成果報告書概要(欧文)」より
Related Report
