Molecular pathogenesis of lumbar disc degeneration

腰椎间盘退变的分子发病机制

• 批准号: 17209050
• 负责人: IKEGAWA Shiro
• 金额: $ 26.29万
• 依托单位: RIKEN
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17209050/
• 关键词: 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

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).

我们旨在确定腰椎间盘病(LDD)/腰椎间盘突出（LDH）的易感基因，并阐明其分子机制。通过对基因及其致病序列变异的分析，我们得到以下结果：1)通过病例对照关联研究，我们确定了软骨中间层蛋白（软骨中间层蛋白）为LDD的易感基因（Seki等）。自然基因，2005)。这是第一个拥有令人信服的功能证据的LDD基因。此外，我们发现CILP与TGF-β结合，抑制其对椎间盘软骨生长和分化的影响。2)我们已经阐明了CILP的转录调控机制（Mori et al.）。生物化学，生物物理，2006)。3)我们检测了编码IX型胶原a2（IX）、a3（IX）链的COL9A2和col9a3的关联，发现日本人可能与欧洲人有不同的易感基因（Seki等）。J Hum Genet, 2006)。此外，我们也没有发现先前报道的基因，MMP3， VDR和AGC1在日本人的LDH中有关联。4)我们发现LDH与XI型胶原蛋白基因有关联。

项目成果

MATN and LAPTM are parts of larger transcription units produced by intergenic splicing:: Intergenic splicing may be a common phenomenon

• DOI: 10.1093/dnares/dsi017
• 发表时间: 2005-10-31
• 期刊: DNA RESEARCH
• 影响因子: 4.1
• 作者: Maeda, Koichi;Horikoshi, Taizo;Ikegawa, Shiro
• 通讯作者: Ikegawa, Shiro

椎間板変性症関連疾患感受性遺伝子およびその用途

椎间盘退变相关疾病易感基因及其用途

• 发表时间: 2005

A large-scale genetic association study of ossification of the posterior longitudinal ligament of the spine

• DOI: 10.1007/s00439-006-0170-9
• 发表时间: 2006-07-01
• 期刊: HUMAN GENETICS
• 影响因子: 5.3
• 作者: Horikoshi, Taizo;Maeda, Koichi;Ikegawa, Shiro
• 通讯作者: Ikegawa, Shiro

Transcriptional regulation of the cartilage intermediate layer protein (CILP) gene

• DOI: 10.1016/j.bbrc.2005.12.159
• 发表时间: 2006-03-03
• 期刊: BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
• 影响因子: 3.1
• 作者: Mori, M;Nakajima, M;Ikegawa, S
• 通讯作者: Ikegawa, S

Association study of COL9A2 with lumbar disc disease in the Japanese population

• DOI: 10.1007/s10038-006-0062-9
• 发表时间: 2006-01-01
• 期刊: JOURNAL OF HUMAN GENETICS
• 影响因子: 3.5
• 作者: Seki, Shoji;Kawaguchi, Yoshiharu;Ikegawa, Shiro
• 通讯作者: Ikegawa, Shiro