| Project/Area Number |
17209050
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | RIKEN |
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Principal Investigator |
IKEGAWA Shiro RIKEN, Laboratory for Bone and Joint diseases, Team leader, 変形性関節症関連遺伝子研究チーム, チームリーダー (30272496)
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| Co-Investigator(Kenkyū-buntansha) |
INABA Ikuyo RIKEN, Laboratory for Bone and Joint diseases, Research associate, 変形性関節症関連遺伝子研究チーム, リサーチアソシエイト (60415081)
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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 |
¥41,080,000 (Direct Cost: ¥31,600,000、Indirect Cost: ¥9,480,000)
Fiscal Year 2006: ¥18,330,000 (Direct Cost: ¥14,100,000、Indirect Cost: ¥4,230,000)
Fiscal Year 2005: ¥22,750,000 (Direct Cost: ¥17,500,000、Indirect Cost: ¥5,250,000)
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| Keywords | Lumbar disc disease / herniation / susceptibility gene / association study / CILP / 椎間板ヘルニア / 分子病態 / ゲノム / SNP / 遺伝子多型 |
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| Research Abstract |
We aimed to identify the susceptibility genes for lumbar disc disease (LDD)/lumbar disc herniation (LDH) and to clarify their molecular mechanism. Through the analysis of the genes and their disease-causing sequence variations, we obtained the following results:
1) By a case-control association study, we identified CILP (cartilage intermediate layer protein) as a susceptibility gene for LDD (Seki et al. Nature Genet, 2005). This is the first LDD gene harboring convincing functional proof. Furthermore, we discovered that CILP binds to TGF-β, and inhibit its effect on growth and differentiation of intervertebral disc cartilage.
2) We have clarified the mechanism of transcriptional regulation of CILP (Mori et al. Biochem Biophys Res Commun,2006).
3) We examined association of COL9A2 and COL9A3that encode a2(IX), a3(IX) chains of type IX collagen, and found that Japanese may have a different susceptibility gene from European (Seki et al. J Hum Genet, 2006). Also, we found no association in the previously reported genes, MMP3, VDR and AGC1 in Japanese LDD.
4) We discovered the association of LDH with type XI collagen gene (manuscript in submission).
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