Transport and binding of tumor necrosis factor-α in articular cartilage depend on its quaternary structure
Author(s)Byun, Sangwon; Sinskey, Yunna L.; Grodzinsky, Alan J.; Lu, Yihong C. S.; Frank, Eliot
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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.
DepartmentMassachusetts Institute of Technology. Center for Biomedical Engineering; Massachusetts Institute of Technology. Department of Biological Engineering; Massachusetts Institute of Technology. Department of Biology; Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science; Massachusetts Institute of Technology. Department of Mechanical Engineering
Archives of Biochemistry and Biophysics
Byun, Sangwon, Yunna L. Sinskey, Yihong C.S. Lu, Eliot H. Frank, and Alan J. Grodzinsky. “Transport and Binding of Tumor Necrosis Factor-α in Articular Cartilage Depend on Its Quaternary Structure.” Archives of Biochemistry and Biophysics 540, no. 1–2 (December 2013): 1–8.
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