Evidence of the TNF-α System in the Human Achilles Tendon: Expression of TNF-α and TNF Receptor at both Protein and mRNA Levels in the Tenocytes
Evidence of the TNF-α System in the Human Achilles Tendon: Expression of TNF-α and TNF Receptor at both Protein and mRNA Levels in the Tenocytes
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DOI：
10.1159/000335475
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发表时间：
2012-01-01
影响因子：
2.7
通讯作者：
Forsgren, Sture
中科院分区：
文献类型：
--
作者：
Gaida, James Edmund;Bagge, Johan;Forsgren, Sture
了解负荷适应性对于肌腱病/肌腱病的预防和治疗至关重要。细胞因子对负荷的反应是机械转导的一种机制。细胞因子肿瘤坏死因子-α(TNF-α)与肌腱病有关，可通过肿瘤坏死因子受体1(INFR1)诱导细胞凋亡。完全缺乏关于跟腱中的肿瘤坏死因子-α系统的信息是一个限制，因为中段跟腱病是非常常见的。目的：检测肿瘤坏死因子-α(INF-α)及其两种受体(TNFR1和TNFR2)在跟腱病组织和对照组织中的表达模式，以生化方法证实肿瘤坏死因子-α在跟腱病组织中的存在。方法：采用原位杂交法检测肿瘤坏死因子-α和肿瘤坏死因子受体1基因的表达。免疫组织化学检测肿瘤坏死因子-α、肿瘤坏死因子受体1和肿瘤坏死因子受体2的表达。应用细胞凋亡标记物。用双抗体夹心法检测肿瘤坏死因子-α。结果：在肌腱病组和对照组肌腱细胞中均可检测到肿瘤坏死因子-α和肿瘤坏死因子受体1基因的表达。两组肌腱细胞均显示出对肿瘤坏死因子-α、肿瘤坏死因子受体1和肿瘤坏死因子受体2的特异性免疫反应。肌腱病标本中变宽/变圆的肌腱细胞免疫反应最强。仅在肌腱病组织中的肌腱细胞亚群中检测到细胞凋亡。肌腱病组织中可检测到肿瘤坏死因子-α。未见炎性细胞。结论：这是人类跟腱中存在干扰素-α系统的第一个证据。这些发现在信使核糖核酸和蛋白质水平以及生化水平上得到了证实。肿瘤坏死因子-α系统原则上仅限于腱细胞。跟腱细胞形态与肿瘤坏死因子-α、肿瘤坏死因子受体1和肿瘤坏死因子受体2的表达模式之间的关系提示，肿瘤坏死因子-α系统可能参与跟腱细胞的激活。版权所有(C)2012年，S.Karger AG，巴塞尔
Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-alpha) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (INFR1). The complete absence of information concerning the TNF-alpha system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent. Purpose: To examine expression patterns of INF-alpha and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-alpha in tendinosis tissue. Methods: TNF-a and TNFR1 mRNA were detected via in situ hybridization. TNF-alpha, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-alpha. Results: TNF-alpha and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-alpha, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-alpha was measurable in tendinosis tissue. Inflammatory cells were not seen. Conclusion: This is the first evidence of the existence of the INF-alpha system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-alpha system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-alpha, TNFR1, and TNFR2 suggests that the TNF-alpha system may be involved in tenocyte activation in Achilles tendinosis. Copyright (c) 2012 S. Karger AG, Basel