Molecular pathogenesis of lumbar disc degeneration

本研究的目的是鉴定腰椎间盘病（LDD）/腰椎间盘突出症（LDH）的易感基因，并阐明其分子机制。通过对这些基因及其致病序列变异的分析，我们获得了以下结果：1）通过病例对照关联研究，我们确定了CILP（软骨中间层蛋白）为LDD的易感基因（Seki et al. Nature Genet，2005）。这是第一个具有令人信服的功能证据的LDD基因。另外，我们还发现CILP与TGF-β结合，抑制其对椎间盘软骨生长和分化的影响（Mori等，Biochem Biophys Res Commun，2006）。3）我们检测了编码IX型胶原的α 2（IX）、α 3（IX）链的COL 9A 2和COL 9A 3的结合，并发现日本人可能具有与欧洲人不同的易感基因（Seki et al. J Genet，2006）。4）发现LDH与Xi型胶原基因相关（投稿中）。

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).