Molecular biologic approach to elucidate intervertebral disc degeneration and establishment of new treatment

腰痛的终生发生率高达60- 80%，日本门诊最常见的主诉是腰痛。腰椎间盘退变是腰椎间盘突出症的主要病因，是由多种细胞因子和酶共同作用的结果。本研究的目的是解释椎间盘退变的原因，并探讨新的细胞因子治疗的可能性。以下是我们目前在椎间盘突出症炎症研究中的新发现。(1)TWEAK是TNF-α家族的成员，它必须分别通过C-Jun或NF-κβ信号通路诱导MMP-3和MCP-1的产生。(2)TSLP必须通过NF-κβ信号通路诱导MCP-1的产生，从而导致Mφ的浸润。(3)TNF-α必须通过TNF-α受体I诱导VEGF，导致新血管形成。然而，这种现象随着年龄的增长而减少。(4)TNF-α和TWEAK诱导MMP-3和MCP-1的表达。然而，这种感应会随着老化而降低。我想继续研究这种精确的机制，并在未来建立新的细胞因子治疗。

Life time occurrence of low back pain goes up to 60-80%, and the most common complaint at outpatient clinic in Japan is LBP. The major cause of LBP is disc degeneration, that is acted by various kinds of cytokines and enzymes. The purpose of the current study is to explain the cause of the disc degenerations, moreover to examine the possibility of new cytokine treatment. The following below are our new findings conducted by the current study in the inflammation of herniated disc. (1) TWEAK, that is the TNF-α family, must induce MMP-3 and MCP-1 through C-Jun or NF-κβ signal pathway respectively. (2) TSLP must induce MCP-1 through NF-κβ signal pathway, resulting in Mφ infiltration. (3) TNF-α must induce VEGF with TNF-α receptor I, resulting in neovascuralization. However this phenomenon is decreased by aging. (4) The induction of MMP-3 and MCP-1 induced by TNF-α and TWEAK. However this induction is decreased by aging. I would like to continue investigation of this precise mechanism, moreover to achieve the establishment of new cytokine treatment in the future.