Advanced oxidation protein products increase TNF-α and IL-1β expression in chondrocytes via NADPH oxidase 4 and accelerate cartilage degeneration in osteoarthritis progression
| Autor: | Wangsheng Jiang, Yi-Qing Wang, Zhongyuan Liu, Si-Yuan Zhu, Zongze Li, Qian Wu, Sheng-Nan Wang, Jianting Chen, Congrui Liao |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male Clinical Biochemistry Interleukin-1beta Osteoarthritis Biochemistry Severity of Illness Index chemistry.chemical_compound Mice 0302 clinical medicine Synovial Fluid lcsh:QH301-705.5 Cells Cultured lcsh:R5-920 NADPH oxidase AOPPs Advanced oxidation protein products biology Chemistry NOX4 Interleukin Middle Aged Osteoarthritis Knee Up-Regulation medicine.anatomical_structure IL-1β Disease Progression OA osteoarthritis Tumor necrosis factor alpha Female lcsh:Medicine (General) Research Paper Adult IL-1β Interleukin (IL)-1β TNF-α tumor necrosis factor (TNF)-α 03 medical and health sciences Chondrocytes medicine Synovial fluid Animals Humans Aged Tumor Necrosis Factor-alpha Cartilage Organic Chemistry NADPH oxidase 4 Advanced oxidation protein products NADPH nicotinamide adenine dinucleotide phosphate medicine.disease Disease Models Animal 030104 developmental biology lcsh:Biology (General) TNF-α Apocynin biology.protein Cancer research 030217 neurology & neurosurgery |
| Zdroj: | Redox Biology Redox Biology, Vol 28, Iss, Pp-(2020) |
| ISSN: | 2213-2317 |
| Popis: | Interleukin (IL)-1β and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1β expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1β in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1β in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1β and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1β in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA. Highlights • AOPPs present in OA joint. • AOPPs increased TNF-α and IL-1β expression in chondrocytes and accelerates progression of OA. • NADPH oxidase inhibitor decreased TNF-α and IL-1β expression and attenuates progression of OA. |
| Databáze: | OpenAIRE |
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