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

分子生物学方法阐明椎间盘退变并建立新的治疗方法

• 批准号: 20591741
• 负责人: HARO Hirotaka
• 金额: $ 3.08万
• 依托单位: University of Yamanashi
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20591741/
• 关键词: TWEAK; MMP-3; MCP-1; 椎間板変性; TNF-α; VEGF; angiogenesis

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.

终生腰痛的发生率高达60%-80%，在日本，门诊最常见的主诉是腰痛。腰椎间盘突出症的主要原因是椎间盘退变，它是由各种细胞因子和酶作用的结果。本研究的目的是解释腰椎间盘退变的原因，并探讨新的细胞因子治疗的可能性。以下是我们目前在腰椎间盘突出症炎症研究中的新发现。(1)TWEK即肿瘤坏死因子-α家族，必须分别通过C-jun或NF-κβ信号通路诱导MMP3和MCP1的表达。(2)TSLP通过NF-κβ信号通路诱导单核细胞趋化蛋白-1，导致M-φ的浸润。(3)肿瘤坏死因子-α必须通过肿瘤坏死因子-α受体I诱导血管内皮生长因子，从而导致新生血管形成。然而，这种现象随着年龄的增长而减少。(4)肿瘤坏死因子-α和TWEK对MMP3和MCP1的诱导作用。然而，这种诱导会随着年龄的增长而减少。我想继续研究这一精确的机制，并在未来实现新的细胞因子治疗的建立。

项目成果

椎間板細胞における炎症性反応の加齢による変化

椎间盘细胞炎症反应的年龄相关变化

• 发表时间: 2010
• 作者: 藤田康稚;安藤隆;大場哲郎;若生政憲;加藤良平;中尾篤人;波呂浩孝
• 通讯作者: 波呂浩孝

A potential role of TSLP in the recruitment of macrophages to mouse interveretebral disc cells via MCP-1 induetion.

TSLP 在通过 MCP-1 诱导向小鼠椎间盘细胞募集巨噬细胞中的潜在作用。

• 发表时间: 2008
• 期刊: Arthritis & Rheumatism 58
• 作者: Tetsuro Ohba;Hirotaka Haro
• 通讯作者: Hirotaka Haro

椎間板由来のサイトカイン産生におけるTNF-αのシグナル伝達経路の解析

椎间盘源性细胞因子产生中TNF-α信号转导通路分析

• 发表时间: 2008
• 作者: 大場哲郎;波呂浩孝
• 通讯作者: 波呂浩孝

炎症による椎間板性腰痛における加齢の影響

衰老对炎症引起的椎间盘源性腰痛的影响

• 发表时间: 2010
• 作者: 藤田康稚;安藤隆;大場哲郎;波呂浩孝
• 通讯作者: 波呂浩孝

老化に伴う椎間板変性の影響について

与衰老相关的椎间盘退变的影响

• 发表时间: 2010
• 作者: 小柳広高、阿江啓介;ほか;藤田康稚
• 通讯作者: 藤田康稚