期刊
JOURNAL OF BIOMEDICAL SCIENCE
卷 18, 期 -, 页码 -出版社
BIOMED CENTRAL LTD
DOI: 10.1186/1423-0127-18-43
关键词
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资金
- National Science Council of Taiwan [NSC98-2314-B-038-005-MY3]
- Taipei Medical University Hospital [96TMU-TMUH-10]
Background: Osteoarthritis (OA) is a degenerative joint disease which affects the entire joint structure, including the synovial membrane. Disease progression was shown to involve inflammatory changes mediated by proteinase-activated receptor (PAR)-2. Previous studies demonstrated that PAR-2 messenger (m) RNA and protein levels increased in OA synovial cells, suggesting that PAR-2 is a potential therapeutic target of the disease. Methods: We designed a PAR-2-inhibiting peptide (PAR2-IP) by changing an isoleucine residue in the PAR-2-activating peptide (PAR2-AP), SLIGKV, to alanine, generating the SLAGKV peptide. We used it to test PAR-2-mediated inflammatory responses, including the expressions of cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-1 and activation of nuclear factor (NF)-kappa B in human synovial cells. As a control, expressions of COX-2 and MMP-1 were induced by trypsin at both the mRNA and protein levels. Results: The PAR2-AP increased the expression of COX-2 more dramatically than that of MMP-1. When we treated cells with the designed PAR2-IP, the trypsin-induced COX-2 level was completely inhibited at a moderate concentration of the PAR2-IP. With further examination of trypsin-induced NF-kappa B activation, we observed sufficient inhibitory effects of the PAR2-IP in synoviosarcoma cells and primary synovial cells from OA patients. Conclusions: Our study suggests that the PAR2-IP inhibits trypsin-induced NF-kappa B activation, resulting in a reduction in inflammatory COX-2 expression in synovial cells. Application of PAR2-IP is suggested as a potential therapeutic strategy for OA.
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