NOD2 signaling pathway is involved in fibronectin fragment-induced pro-catabolic factor expressions in human articular chondrocytes
| Autor: | Min Ha Choi, Hyun Sook Hwang, Mi Hyun Lee, Hyun Ah Kim |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Immunoprecipitation
Interleukin-1beta Nod2 Signaling Adaptor Protein Biochemistry NOD2 03 medical and health sciences Chondrocytes Nod1 Signaling Adaptor Protein Osteoarthritis Gene expression NOD1 Humans Gene silencing Molecular Biology Cells Cultured Fibronectin fragments IL-6 0303 health sciences Gene knockdown IL-8 biology Interleukin-6 Tumor Necrosis Factor-alpha Chemistry Interleukin-8 030302 biochemistry & molecular biology Metalloendopeptidases Articles General Medicine Peptide Fragments Toll-Like Receptor 2 digestive system diseases Fibronectins Cell biology Matrix metalloproteinase Fibronectin Cartilage biology.protein Cytokines Joints Signal transduction Signal Transduction Transforming growth factor |
| Zdroj: | BMB Reports |
| ISSN: | 1976-670X |
| DOI: | 10.5483/bmbrep.2019.52.6.165 |
| Popis: | The nucleotide-binding and oligomerization domain (NOD) is an innate pattern recognition receptor that recognizes pathogen- and damage-associated molecular patterns. The 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 was 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 RNAs were used for knockdown of NOD2 and toll-like receptor 2 (TLR-2). An immunoprecipitation assay was performed to examine protein interactions. The NOD2 levels in human OA cartilage were much higher than in normal cartilage. NOD1 and NOD2 expression, as well as pro-inflammatory cytokines, including interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α), were upregulated by 29-kDa FN-f in human chondrocytes. NOD2 silencing showed that NOD2 was involved in the 29-kDa FN-f-induced expression of TLR-2. Expressions of IL-6, IL-8, matrix metalloproteinase (MMP)-1, -3, and -13 were also suppressed by TLR-2 knockdown. Furthermore, NOD2 and TLR-2 knockdown data demonstrated that both NOD2 and TLR-2 modulated the expressions of their adaptors, receptorinteracting 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 the TLR-2 signaling pathway, and activated nuclear factor-κB (NF-κB), subsequently leading to increased expressions of pro-inflammatory cytokines and cartilagedegrading enzymes. These results demonstrate that 29-kDa FN-f modulated pro-catabolic responses via cross-regulation of NOD2 and TLR-2 signaling pathways. [BMB Reports 2019; 52(6): 373-378]. |
| Databáze: | OpenAIRE |
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