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http://ir.nhri.org.tw/handle/3990099045/12032
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| Title: | Anti-inflammatory and anti-osteoarthritis effects of Cm-02 and Ck-02 |
| Authors: | Ho, YJ;Lu, JW;Ho, LJ;Lai, JH;Huang, HS;Lee, CC;Lin, TY;Lien, SB;Lin, LC;Chen, LW;Gong, Z;Shen, MC;Liu, FC |
| Contributors: | Institute of Cellular and Systems Medicine |
| Abstract: | Osteoarthritis (OA) is a common degenerative joint disease characterized by progressive deterioration of articular cartilage. There have been reports that small molecule inhibitors have anti-osteoarthritis effects; however, the effects of 3-(4-chloro-2-fluorophenyl)-6-(2,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Cm-02) and 6-(2,4-difluorophenyl)-3-(3,4-difluorophenyl)-2H-benzo[e] [1,3]oxazine-2,4(3H)-dione (Ck-02), small molecule inhibitors which share many structural similarities with quercetin (a potent anti-inflammatory flavonoid), remain unclear. In this study, TNF-alpha-stimulated porcine and human chondrocyte models were used to investigate the inhibitory effects of Cm-02 and Ck-02 on the molecular mechanisms underlying the anti-OA effects. TNF-alpha was used to stimulate porcine and human chondrocytes to mimic immunomodulatory potency in-vitro. Anti-osteoarthritic effects were characterized in terms of protein and mRNA levels associated with the pathogenesis of OA. We also examined (1) the inducible nitric oxide synthase (iNOS)-nitric oxide (NO) system in cultured chondrocytes, (2) matrix metalloproteinases (MMPs) in cultured chondrocytes, and (3) aggrecan degradation in cartilage explants. Finally, we tested the activation of nuclear factor-kappaB (NF-kappaB), interferon regulatory factor-1 (IRF-1), and activate the protein-1 (AP-1), and we tested the signal transduction and activation of transcription-3 (STAT-3). Our results indicate that, in chondrocytes, Cm-02 and Ck-02 inhibit TNF-alpha induced NO production, iNOS, MMP, the expression of disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS), and the enzyme activity of MMP-13. Furthermore, both Cm-02 and Ck-02 were found to stimulate TNF-alpha, which has been shown to suppress the activation of several transcription factors, including NF-kappaB, STAT-3, and IRF-1 in porcine and human chondrocytes. Cm-02 and Ck-02 were also found to help prevent the release of proteoglycans from cartilage explants. Our findings demonstrate that both Cm-02 and Ck-02 have potent anti-inflammatory activities and the ability to protect cartilage in an OA cell model. These findings indicate that Cm-02 and Ck-02 have the potential to be further developed for the therapeutic treatment of OA. |
| Date: | 2019-09 |
| Relation: | Biochemical and Biophysical Research Communications. 2019 Sep;517(1):155-163. |
| Link to: | http://dx.doi.org/10.1016/j.bbrc.2019.07.036 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0006-291X&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000480371200023 |
| Cited Times(Scopus): | https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85069922770 |
| Appears in Collections: | [何令君] 期刊論文
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| PUB31353084.pdf | | 1831Kb | Adobe PDF | 357 | View/Open |
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