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https://ir.csmu.edu.tw:8080/ir/handle/310902500/18128
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| Title: | Upregulation of urokinase-type plasminogen activator and inhibitor and gelatinase expression via 3 mitogen-activated protein kinases and PI3K pathways during the early development of osteoarthritis |
| Authors: | Hsieh, Y.-S.;Yang, S.-F.;Lue, K.-H.;Chu, S.-C.;Li, T.-J.;Lu, K.-H. |
| Keywords: | Matrix metalloproteinase;Osteoarthritis;Plasminogen activator inhibitor;Signaling pathway |
| Date: | 2007 |
| Issue Date: | 2017-08-07T09:14:03Z (UTC)
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| ISSN: | 0315162X |
| Abstract: | Objective. To examine whether upregulation of urokinase-type plasminogen activator (u-PA), PA inhibitor-1 (PAI-1), and gelatinases [matrix metalloproteinase (MMP)-2 and MMP-9] in early knee osteoarthritis (OA) of humans occurs through 3 major mitogen-activated protein kinases (MAPK): extracellular signal-regulated protein kinase (ERK), c-Jun N-terminal kinase (JNK) and p38 kinase signaling pathways, and the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Methods. Enzyme linked immunosorbent assay and gelatin zymography were used to investigate the effects of ERK 1/2 inhibitor U0126, JNK and p38 inhibitor SB203580, and PI3K inhibitor LY294002 on the secretion of u-PA, PAI-1, MMP-2, and MMP-9 in early osteoarthritic tissue cultures, with or without interleukin 1α (IL-1α) and lipopolysaccharide (LPS) induction. Results. Our findings were: (1) latent and active forms of MMP-9 secretion in synovial and some meniscal cultures were inhibited significantly by U0126, SB203580, and LY294002; (2) latent and active forms of MMP-2 secretion were also inhibited significantly by U0126 and LY294002, but not by SB203580, except for active MMP-2 in synovial cultures; (3) a similar observation was seen in IL-1α-and LPS-treated cultures; and (4) U0126, SB203580, and LY294002 significantly decreased u-PA and PAI-1 levels in all cultures in the presence or absence of IL-1α and LPS. Conclusion. MAPK ERK, JNK, and p38 signaling pathways and the PI3K signaling pathway are involved in upregulation of u-PA, PAI-1, and gelatinase expression during early development of knee OA. Thus, blocking PA/plasmin and gelatinase expression by novel physiologic and pharmacological inhibitors could be an important therapeutic or preventive approach for early OA. |
| URI: | http://dx.doi.org/
https://www.scopus.com/inward/record.uri?eid=2-s2.0-34247377817&partnerID=40&md5=7169e4f4b2e6043de31c8557bdc70ff6
https://ir.csmu.edu.tw:8080/ir/handle/310902500/18128 |
| Relation: | Journal of Rheumatology 34(4),785-793 |
| Appears in Collections: | [醫學系] 期刊論文
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