BMB Reports Papers in Press available online.

Search Papers In Press
This galley proof is being listed electronically before publishing the final manuscript (It's not final version).

 
NOD2 signaling pathway was involved in fibronectin fragment-induced pro-catabolic factor expressions in human articular chondrocytes
Hyun Sook Hwang1,2,#, Mi Hyun Lee1,2,#, Min Ha Choi1,2, Hyun Ah Kim1,2,*
1Department of Internal Medicine, Hallym University Sacred Heart Hospital,
2Institute for Skeletal Aging, Hallym University
Abstract
Nucleotide-binding and oligomerization domain (NOD) is innate pattern recognition receptor that recognizes pathogen-associated molecular patterns and damage-associated molecular patterns. 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) is a matrix degradation product found in the synovial fluids of patients with osteoarthritis (OA). We investigated whether NOD2 is involved in 29-kDa FN-f-induced pro-catabolic gene expression in human chondrocytes. The expression of mRNA and protein was measured using quantitative real-time polymerase chain reaction (qrt-PCR), and western blot analysis. Small interfering RNA was used for knockdown of NOD2 and toll-like receptor 2 (TLR-2). Immunoprecipitation assay was performed to examine interaction of proteins. NOD2 level in human OA cartilage was much higher than in normal cartilage. NOD1 and NOD2 expressions were upregulated by 29-kDa FN-f in human chondrocytes but also pro-inflammatory cytokines, including interleukin-1beta (IL-1モ) and tumor necrosis factor-alpha (TNF-メ). NOD2 silencing showed that NOD2 was involved in 29-kDa FN-f-induced expressions of TLR-2 as well as IL-6, IL-8, matrix metalloproteinase (MMP)-1, -3, and -13, which were also suppressed by TLR-2 knockdown. Furthermore, NOD2 or TLR-2 knockdown data demonstrated that both NOD2 and TLR-2 modulated the expressions of their adaptors receptor-interacting protein 2 (RIP2) and myeloid differentiation 88 in 29-kDa FN-f-treated chondrocytes. 29-kDa FN-f enhanced the interaction of NOD2, RIP2 and transforming growth factor beta-activated kinase 1 (TAK1), an indispensable signaling intermediate in TLR-2 signaling pathway, and activated nuclear factor-リB (NF-リB), subsequently leading to increased expressions of pro-inflammatory cytokines and cartilage degrading enzymes. These results demonstrate that 29-kDa FN-f modulated pro-catabolic responses via cross-regulation of NOD2 and TLR-2 signaling pathways.
Abstract, Accepted Manuscript(in press) [Submitted on July 20, 2018, Accepted on September 20, 2018]
  Copyright © KSBMB. All rights reserved. / Powered by INFOrang.co., Ltd