Transport and binding of tumor necrosis factor-α in articular cartilage depend on its quaternary structure.
Transport and binding of tumor necrosis factor-α in articular cartilage depend on its quaternary structure.
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DOI：
10.1016/j.abb.2013.10.003
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发表时间：
2013-12
影响因子：
3.9
通讯作者：
Grodzinsky, Alan J.
中科院分区：
文献类型：
--
作者：
Byun, Sangwon;Sinskey, Yunna L.;Lu, Yihong C. S.;Frank, Eliot H.;Grodzinsky, Alan J.
肿瘤坏死因子-α对软骨基质降解的影响是通过其在组织的细胞外基质内的转运和结合来实现的，而细胞外基质的转运和结合则介导了对细胞受体的可获得性。由于生物活性形式的肿瘤坏死因子α是单体亚基的同源三聚体，在软骨内转运过程中，三聚体和单体之间的转换可能会影响与细胞外基质的结合，从而影响软骨内的生物活性。考虑到细胞因子的四级结构，我们研究了肿瘤坏死因子α在软骨中的转运和结合。竞争性结合分析显示肿瘤坏死因子α显著结合在软骨组织中，导致摄取增强。然而，在研究中，肿瘤坏死因子α以三聚体形式存在，三聚体肿瘤坏死因子α的结合可以忽略不计。因此，肿瘤坏死因子α与细胞外基质的结合与单体形式有关。用胰酶处理软骨组织不会破坏肿瘤坏死因子α的结合，胰酶去除了蛋白多糖和糖蛋白，但保留了胶原网络的完整。因此，蛋白多糖在骨关节炎过程中的丢失只会改变肿瘤坏死因子α的被动扩散，而不会改变其与剩余基质的结合作用。我们的结果表明，基质结合和肿瘤坏死因子α的三聚单体转化在调节生物活性肿瘤坏死因子α在软骨内的可及性方面起着至关重要的作用。
The effect of tumor necrosis factor-α (TNFα) on cartilage matrix degradation is mediated by its transport and binding within the extracellular matrix (ECM) of the tissue, which mediates availability to cell receptors. Since the bioactive form of TNFα is a homotrimer of monomeric subunits, conversion between trimeric and monomeric forms during intratissue transport may affect binding to ECM and, thereby, bioactivity within cartilage. We studied the transport and binding of TNFα in cartilage, considering the quaternary structure of this cytokine. Competitive binding assays showed significant binding of TNFα in cartilage tissue, leading to an enhanced uptake. However, studies in which TNFα was cross-linked to remain in the trimeric form revealed that the binding of trimeric TNFα was negligible. Thus, binding of TNFα to ECM was associated with the monomeric form. Binding of TNFα was not disrupted by pre-treating cartilage tissue with trypsin, which removes proteoglycans and glycoproteins but leaves the collagen network intact. Therefore, proteoglycan loss during osteoarthritis should only alter the passive diffusion of TNFα but not its binding interaction with the remaining matrix. Our results suggest that matrix binding and trimer-monomer conversion of TNFα both play crucial roles in regulating the accessibility of bioactive TNFα within cartilage.
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影响因子：
5
作者：
Goldring, M B
通讯作者：
Goldring, M B
影响因子：
4.8
作者：
Bhakta, NR;Garcia, AM;Morales, TI
通讯作者：
Morales, TI
肿瘤坏死因子的生物活性因子的可溶受体的稳定性。
DOI：
10.1084/jem.175.2.323
发表时间：
1992-02-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Aderka D;Engelmann H;Maor Y;Brakebusch C;Wallach D
通讯作者：
Wallach D
影响因子：
3.4
作者：
MAROUDAS, A
通讯作者：
MAROUDAS, A
影响因子：
4.8
作者：
Cameron, M;Buchgraber, A;Evans, CH
通讯作者：
Evans, CH