Down-regulation of protease-activated receptor 2 ameliorated osteoarthritis in rats through regulation of MAPK/NF-κB signaling pathway in vivo and in vitro
Autor: | Chenglong Pang, Xinqiang Wang, Huimin Ding, Jian-jun Wei, Chen Hui, Wei Juncheng, Peng Junyang, Shichang Yan |
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Rok vydání: | 2020 |
Předmět: |
Male
0301 basic medicine MAPK/ERK pathway Agonist Cell Homeostasis & Autophagy China MAP Kinase Signaling System medicine.drug_class p38 mitogen-activated protein kinases Biophysics p38 Mitogen-Activated Protein Kinases Biochemistry Rats Sprague-Dawley MAPK/NF-kB signaling pathway 03 medical and health sciences Chondrocytes 0302 clinical medicine Protease-activated receptor 2 In vivo Osteoarthritis Matrix Metalloproteinase 13 Autophagy medicine Animals Receptor PAR-2 Receptor Molecular Biology Diagnostics & Biomarkers Research Articles Tumor Necrosis Factor-alpha Chemistry NF-kappa B Antagonist Cell Biology Rats Cell biology 030104 developmental biology Cyclooxygenase 2 030220 oncology & carcinogenesis Female Matrix Metalloproteinase 1 Signal transduction Biotechnology Signal Transduction |
Zdroj: | Bioscience Reports |
ISSN: | 1573-4935 0144-8463 |
Popis: | Recently, protease-activated receptor 2 (PAR2) has been proved to be involved in the inflammatory response including osteoarthritis (OA). In the present study, we found that PAR2 antagonist could remarkably improve the pathological condition of OA rats in vivo. In addition, we also found that PAR2 antagonist could suppress the production of inflammatory factors (TNF-α and Cox-2), decrease the levels of MMP-1 and MMP-13, and restrain the levels of P62 proteins and aggravate the expression of LC3-II both in vivo and in vitro. Besides, in vitro, PAR2 antagonist could increase the proliferation and colony formation of chondrocytes induced with IL-1β. Moreover, PAR2 antagonist could decrease the expression of expressions of p-p38, p-IκBα and p-NF-κB in vitro. However, PAR2 agonist exhibited the opposite effects. Furthermore, SB203580, a p38 MAPK inhibitor, could remarkably promote the proliferation of chondrocytes induced with IL-1β, could alleviate the production of TNF-α and Cox-2, could down-regulate the protein expressions of MMP-1 and MMP-13, and could decrease the expression of P62 and increase the expressions of LC3-II of chondrocytes induced with IL-1β. Importantly, SB203580 could reverse the effects of PAR2 agonist on the functions of chondrocytes induced with IL-1β. Taken together, the present data suggest that down-regulation of PAR2 can ameliorate OA through inducing autophagy via regulation of MAPK/NF-κB signaling pathway in vivo and in vitro, and PAR2 can be considered as a potential candidate to treat OA. |
Databáze: | OpenAIRE |
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