Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways
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Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration.
- Aikawa, Y., Morimoto, K., Yamamoto, T., Chaki, H., Hashiramoto, A., Narita, H., Hirono, S., and Shiozawa, S., Treatment of arthritis with a selective inhibitor of c-Fos/activator protein-1. Nat. Biotechnol., 26, 817–823 (2008). CrossRef
- Barksby, H. E., Hui, W., Wappler, I., Peters, H. H., Milner, J. M., Richards, C. D., Cawston, T. E., and Rowan, A. D., Interleukin-1 in combination with oncostatin M upregulates multiple genes in chondrocytes: implications for cartilage destruction and repair. Arthritis Rheum., 54, 540–550 (2006). CrossRef
- Behera, A. K., Thorpe, C. M., Kidder, J. M., Smith, W., Hildebrand, E., and Hu, L. T., Borrelia burgdorferi-induced expression of matrix metalloproteinases from human chondrocytes requires mitogen-activated protein kinase and janus kinase/signal transducer and activator of transcription signaling pathways. Infect. Immun., 72, 2864–2871 (2004). CrossRef
- Boileau, C., Pelletier, J. P., Tardif, G., Fahmi, H., Laufer, S., Lavigne, M., and Martel-Pelletier, J., The regulation of human MMP-13 by licofelone, an inhibitor of cyclo-oxygenases and 5-lipoxygenase, in human osteoarthritic chondrocytes is mediated by the inhibition of the p38 MAP kinase signalling pathway. Ann. Rheum. Dis., 64, 891–898(2005). CrossRef
- Catterall, J. B., Carrère, S., Koshy, P. J., Degnan, B. A., Shingleton, W. D., Brinckerhoff, C. E., Rutter, J., Cawston, T. E., and Rowan, A. D., Synergistic induction of matrix metalloproteinase 1 by interleukin-1 and oncostatin M in human chondrocytes involved signal transducer and activation of transcription and activator protein 1 transcription factors via a novel mechanism. Arthritis Rheum., 44,2296–2310 (2001). CrossRef
- Cowell, S., Knäuper, V., Stewart, M. L., D’Ortho, M. P., Stanton, H., Hembry, R. M., López-Otín, C., Reynolds, J. J., and Murphy, G., Induction of matrix metalloproteinase activation cascades based on membrane-type 1 matrix metalloproteinase: associated activation of gelatinase A, gelatinase B and collagenase 3. Biochem. J., 331, 453–458 (1998).
- Elliott, S., Hays, E., Mayor, M., Sporn, M., and Vincenti, M., The triterpenoid CDDO inhibits expression of matrix metalloproteinase-1, matrix metalloproteinase-13 and Bcl-3 in primary human chondrocytes. Arthritis Res. Ther., 5, R285–R291 (2003). CrossRef
- El Mabrouk, M., Sylvester, J., and Zafarullah, M., Signaling pathways implicated in oncostatin M-induced aggrecanase-1 and matrix metalloproteinase-13 expression in human articular chondrocytes. Biochim. Biophys. Acta, 1773, 309–320 (2007). CrossRef
- Fan, Z., Bau, B., Yang, H., Soeder, S., and Aigner, T., Freshly isolated osteoarthritic chondrocytes are catabolically more active than normal chondrocytes, but less responsive to catabolic stimulation with interleukin-1ß. Arthritis Rheum., 52, 136–143 (2005). CrossRef
- Fan, Z., Yang, H., Bau, B., Söder, S., and Aigner, T., Role of mitogen-activated protein kinases and NF-κB on IL-1β-induced effects on collagen type II, MMP-1 and 13 mRNA expression in normal articular human chondrocytes. Rheumatol. Int., 26, 900–903 (2006). CrossRef
- Gebauer, M., Saas, J., Sohler, F., Haag, J., Söder, S., Pieper, M., Bartnik, E., Beninga, J., Zimmer, R., and Aigner, T., Comparison of the chondrosarcoma cell line SW1353 with primary human adult articular chondrocytes with regard to their gene expression profile and reactivity to IL-1β. Osteoarthritis Cartilage, 13, 697–708 (2005). CrossRef
- Heinrich, P. C., Behrmann, I., Müller-Newen, G., Schaper, F., and Graeve, L., Interleukin-6-type cytokine signalling through the gp130/Jak/STAT pathway. Biochem. J., 334, 297–314 (1998).
- Ho, L. J., Lin, L. C., Hung, L. F., Wang, S. J., Lee, C. H., Chang, D. M., Lai, J. H., and Tai, T. Y., Retinoic acid blocks pro-inflammatory cytokine-induced matrix metalloproteinase production by down-regulating JNK-AP-1 signaling in human chondrocytes. Biochem. Pharmacol., 70, 200–208 (2005). CrossRef
- Johnson, A. R., Pavlovsky, A. G., Ortwine, D. F., Prior, F., Man, C. F., Bornemeier, D. A., Banotai, C. A., Mueller, W. T., McConnell, P., Yan, C., Baragi, V., Lesch, C., Roark, W. H., Wilson, M., Datta, K., Guzman, R., Han, H. K., and Dyer, R. D., Discovery and characterization of a novel inhibitor of matrix metalloprotease-13 that reduces cartilage damage in vivo without joint fibroplasia side effects. J. Biol. Chem., 282, 27781–27791 (2007). CrossRef
- Legendre, F., Bogdanowicz, P., Boumediene, K., and Pujol, J.-P., Role of interleukin 6 (IL-6)/IL-6R-induced signal transducers and activators of transcription and mitogen-activated protein kinase/extracellular signal-related kinase in upregulation of matrix metalloproteinase and ADAMTS gene expression in articular chondrocytes. J. Rheumatol., 32, 1307–1316 (2005).
- Li, W. Q., Dehnade, F., and Zafarullah, M., Oncostatin Minduced matrix metalloproteinase and tissue inhibitor of mettaloproteinase-3 genes expression in chondrocytes requires Janus kinase/STAT signaling pathway. J. Immunol., 166, 3491–3498 (2001).
- Liacini, A., Sylvester, J., Li, W. Q., and Zafarullah, M., Mithramycin downregulates proinflammatory cytokine-induced matrix metalloproteinase gene expression in articular chondrocytes. Arthritis Res. Ther., 7, R777–783 (2005). CrossRef
- Mengshol, J. A., Vincenti, M. P., Coon, C. I., Barchowsky, A., and Brinckerhoff, C. E., Interleukin-1 induction of collagenase 3 (matrix metalloproteinase 13) gene expression in chondrocytes requires p38, c-Jun N-terminal kinase, and nuclear factor κB: differential regulation of collagenase 1 and collagenase 3. Arthritis Rheum., 43, 801–811 (2000). CrossRef
- Mengshol, J. A., Vincenti, M. P., and Brinckerhoff, C. E., IL-1 induces collagenase-3 (MMP-13) promoter activity in stably transfected chondrocytic cells: requirement for Runx-2 and activation by p38 MAPK and JNK pathways. Nucleic Acids Res., 29, 4361–4372 (2001). CrossRef
- Mitchell, P. G., Magna, H. A., Reeves, L. M., Lopresti-Morrow, L. L., Yocum, S. A., Rosner, P. J., Geoghegan, K. F., and Hambor, J. E., Cloning, expression, and type II collagenolytic activity of matrix metalloproteinase-13 from human osteoarthritic cartilage. J. Clin. Invest., 97, 761–768 (1996). CrossRef
- Mosmann, T., Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J. Immunol. Methods, 65, 55–63 (1983). CrossRef
- Pei, Y., Harvey, A., Yu, X. P., Chandrasekhar, S., and Thirunavukkarasu, K., Differential regulation of cytokineinduced MMP-1 and MMP-13 expression by p38 kinase inhibitors in human chondrosarcoma cells: potential role of Runx2 in mediating p38 effects. Osteoarthritis Cartilage, 14, 749–758 (2006). CrossRef
- Pelletier, J. P., McCollum, R., Cloutier, J. M., and Martel-Pelletier, J., Synthesis of metalloproteases and interleukin 6 (IL-6) in human osteoarthritic synovial membrane is an IL-1 mediated process. J. Rheumatol. Suppl., 43, 109–114 (1995).
- Pfander, D., Heinz, N., Rothe, P., Carl, H. D., and Swoboda, B., Tenascin and aggrecan expression by articular chondrocytes is influenced by interleukin 1β: a possible explanation for the changes in matrix synthesis during osteoarthritis. Ann. Rheum. Dis., 63, 240–244 (2004). CrossRef
- Rose-John, S., Scheller, J., Elson, G., and Jones, S. A., Interleukin-6 biology is coordinated by membrane-bound and soluble receptors: role in inflammation and cancer. J. Leukoc. Biol., 80, 227–236 (2006). CrossRef
- Rowan, A. D., Koshy, P. J., Shingleton, W. D., Degnan, B. A., Heath, J. K., Vernallis, A. B., Spaull, J. R., Life, P. F., Hudson, K., and Cawston, T. E., Synergistic effects of glycoprotein 130 binding cytokines in combination with interleukin-1 on cartilage collagen breakdown. Arthritis Rheum., 44, 1620–1632 (2001). CrossRef
- Saha, N., Moldovan, F., Tardif, G., Pelletier, J. P., Cloutier, J. M., and Martel-Pelletier, J., Interleukin-1ß-converting enzyme/caspase-1 in human osteoarthritic tissues: localization and role in the maturation of interleukin-1ß and interleukin-18. Arthritis Rheum., 42, 1577–1587 (1999). CrossRef
- Senolt, L., Grigorian, M., Lukanidin, E., Simmen, B., Michel, B. A., Pavelka, K., Gay, R. E., Gay, S., and Neidhart, M., S100A4 is expressed at site of invasion in rheumatoid arthritis synovium and modulates production of matrix metalloproteinases. Ann. Rheum. Dis., 65, 1645–1648 (2006). CrossRef
- Takaishi, H., Kimura, T., Dalal, S., Okada, Y., and D’Armiento, J., Joint diseases and matrix metalloproteinases: a role for MMP-13. Curr. Pharm. Biotechnol., 9, 47–54 (2008). CrossRef
- Vidal, A., Sabatini, M., Rolland-Valognes, G., Renard, P., Madelmont, J. C., and Mounetou, E., Synthesis and in vitro evaluation of targeted tetracycline derivatives: effects on inhibition of matrix metalloproteinases. Bioorg. Med. Chem., 15, 2368–2374 (2007). CrossRef
- Vincenti, M. P. and Brinckerhoff, C. E., Early response genes induced in chondrocytes stimulated with the inflammatory cytokine interleukin-1β. Arthritis Res., 3, 381–388 (2001). CrossRef
- Wada, Y., Shimada, K., Sugimoto, K., Kimura, T., and Ushiyama, S., Novel p38 mitogen-activated protein kinase inhibitor R-130823 protects cartilage by down-regulating matrix metalloproteinase-1, -13 and prostaglandin E2 production in human chondrocytes. Int. Immunopharmacol., 6, 144–155 (2006). CrossRef
- Wen, D., Nong, Y., Morgan, J. G., Gangurde, P., Bielecki, A., Dasilva, J., Keaveney, M., Cheng, H., Fraser, C., Schopf, L., Hepperle, M., Harriman, G., Jaffee, B. D., Ocain, T. D., and Xu, Y., A selective small molecule IκB kinase β inhibitor blocks nuclear factor κB-mediated inflammatory responses in human fibroblast-like synoviocytes, chondrocytes and mast cells. J. Pharmacol. Exp. Ther., 317, 989–1001 (2006). CrossRef
- Wimsey, S., Lien, C. F., Sharma, S., Brennan, P. A., Roach, H. I., Harper, G. D., and Górecki, D. C., Changes in immunolocalisation of beta-dystroglycan and specific degradative enzymes in the osteoarthritic synovium. Osteoarthritis Cartilage, 14, 1181–1188 (2006). CrossRef
- Yammani, R. R., Long, D., and Loeser, R. F., Interleukin-7 stimulates secretion of S100A4 by activating the Jak/STAT signaling pathway in human articular chondrocytes. Arthritis Rheum., 60, 792–800 (2009). CrossRef
- Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways
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