Analysis of tissue distribution of TNF-α, TNF-α-receptors, and the activating TNF-α-converting enzyme suggests activation of the TNF-α system in the aging intervertebral disc

Analysis of tissue distribution of TNF-α, TNF-α-receptors, and the activating TNF-α-converting enzyme suggests activation of the TNF-α system in the aging intervertebral disc
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DOI:
10.1196/annals.1397.069
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发表时间:
2007-01-01
期刊:
SIGNAL TRANSDUCTION PATHWAYS, PT D
影响因子:
--
通讯作者:
Boos, Norbert
Boos, Norbert
中科院分区:
其他
文献类型:
--
作者:
Bachmeier, Beatrice E.;Nerlich, Andreas G.;Boos, Norbert

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我们化学分析了TNF-α、其受体TNF-RI和-RII以及TNF-α激活酶TACE在人尸检(n = 63)和手术(n = 35)腰椎间盘样本中的表达和定位。同时,通过逆转录酶-聚合酶链反应(RT-PCR)定量TNF-α-mRiNA。对所有样本进行形态测定评估,以确定椎间盘不同解剖区域中阳性标记细胞的比例。我们检测到一个显着的和可比的表达所有四个参数开始在年轻的成年人年龄(c。18岁),并且在髓核中最广泛。这一水平在较老年龄的光盘中略有下降。纤维环含有显着较少的标记细胞。与此雅阁的是,在大多数化学性TNF-α表达的病例中,TNF-α转录本的数量升高。我们提供了明确的证据表明,TNF-α在年龄增加的椎间盘中表达,这与椎间盘退变的组织形态学体征相关。因此,TNF-α似乎被激活(通过转化酶TACE),并通过其受体在人腰椎间盘组织中具有生物活性。
We immunohistochemically analyzed the expression and localization of TNF-alpha, its receptors TNF-RI and -RII, and the TNF-alpha-activating enzyme TACE in human autopsy (n = 63) and surgical (n = 35) lumbar intervertebral disc samples. In parallel, the TNF-alpha-mRiNA was quantified by reverse transcriptase-polymerase chain reaction (RT-PCR). All samples were morphometrically evaluated for the proportion of positively labeled cells in the different anatomical regions of the disc. We detected a significant and comparable expression of all four parameters beginning in young adult age (c. 18 years) and being most extensive in the nucleus pulposus. This level was slightly reduced in older age discs. The annulus fibrosus contained significantly less labeled cells. In accord, the number of TNF-alpha-transcripts was elevated in most cases with immunohistochernical TNF-alpha expression. We provide clear evidence that TNF-ot is expressed in discs of increasing age, which correlates with histomorphological signs of disc degeneration. In consequence, TNF-alpha seems to be activated (by the converting enzyme TACE) and biologically active through its receptors in human lumbar disc tissue.