Abstract
It has been reported that matrix metalloproteinases (MMPs) are induced by many cytokines, and they are involved in various inflammatory processes, including periodontitis. However, the effects of interleukin-1β (IL-1β) on MMP-9 expression in cementoblasts, the cells responsible for cementum production, remain largely unknown. In this study, we used qPCR and gelatin zymogram analysis to show that IL-1β upregulated MMP-9 expression in cementoblast-derived cell line. Several signaling pathways, such as ERK1/2, JNK, p38, and AP-1 (c-Fos and ATF-2), were activated in response to IL-1β stimulation. Furthermore, enhancement of AP-1 activity by IL-1β was further confirmed by the AP-1 reporter assay and the electrophoretic mobility shift assay (EMSA). Pretreatment with specific inhibitors of ERK1/2 (U0126), JNK (SP600125), and AP-1 (tanshinone IIA) attenuated IL-1β-induced MMP-9 expression. In addition, inhibitors of ERK1/2 (U0126) and JNK (SP600125) attenuated IL-1β-enhanced AP-1 activity. This suggested that IL-1β stimulated AP-1 activation, at least partially, through ERK1/2 and JNK signaling pathways. Moreover, we found that IL-1β also upregulated the expression of MMP-13 and enhanced MMP-mediated degradation of type I collagen. Collectively, these results suggested that IL-1β induced MMP-9 expression by activation of AP-1 through the ERK1/2 and JNK signaling pathways in cementoblast-derived cell line and enhanced MMP-mediated collagen degradation possibly by MMP-13 and MMP-9.
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References
Bartold, P.M., and T.E. Van Dyke. 2013. Periodontitis: a host-mediated disruption of microbial homeostasis. Unlearning learned concepts. Periodontology 2000 62 (1): 203–217. https://doi.org/10.1111/j.1600-0757.2012.00450.x.
Darveau, R.P. 2010. Periodontitis: a polymicrobial disruption of host homeostasis. Nature Reviews. Microbiology 8 (7): 481–490. https://doi.org/10.1038/nrmicro2337.
Giannobile, W.V. 2008. Host-response therapeutics for periodontal diseases. Journal of Periodontology 79 (8 Suppl): 1592–1600. https://doi.org/10.1902/jop.2008.080174.
Ebersole, J.L., and M.A. Taubman. 1994. The protective nature of host responses in periodontal diseases. Periodontol 2000 5: 112–141.
Sapna, G., S. Gokul, and K. Bagri-Manjrekar. 2014. Matrix metalloproteinases and periodontal diseases. Oral Diseases 20 (6): 538–550. https://doi.org/10.1111/odi.12159.
Parks, W.C., C.L. Wilson, and Y.S. Lopez-Boado. 2004. Matrix metalloproteinases as modulators of inflammation and innate immunity. Nature Reviews Immunology 4 (8): 617–629. https://doi.org/10.1038/nri1418.
Page-McCaw, A., A.J. Ewald, and Z. Werb. 2007. Matrix metalloproteinases and the regulation of tissue remodelling. Nature Reviews Molecular Cell Biology 8 (3): 221–233. https://doi.org/10.1038/nrm2125.
Bernard, Y., C. Melchior, E. Tschirhart, and J.L. Bueb. 2008. Co-cultures of human coronary smooth muscle cells and dimethyl sulfoxide-differentiated HL60 cells upregulate ProMMP9 activity and promote mobility-modulation by reactive oxygen species. Inflammation 31 (5): 287–298. https://doi.org/10.1007/s10753-008-9077-z.
Pasternak, B., and P. Aspenberg. 2009. Metalloproteinases and their inhibitors-diagnostic and therapeutic opportunities in orthopedics. Acta Orthopaedica 80 (6): 693–703. https://doi.org/10.3109/17453670903448257.
Arpino, V., M. Brock, and S.E. Gill. 2015. The role of TIMPs in regulation of extracellular matrix proteolysis. Matrix Biology 44-46: 247–254. https://doi.org/10.1016/j.matbio.2015.03.005.
Hernandez, M., M.A. Valenzuela, C. Lopez-Otin, J. Alvarez, J.M. Lopez, R. Vernal, and J. Gamonal. 2006. Matrix metalloproteinase-13 is highly expressed in destructive periodontal disease activity. Journal of Periodontology 77 (11): 1863–1870. https://doi.org/10.1902/jop.2006.050461.
Hernandez, M., N. Dutzan, J. Garcia-Sesnich, L. Abusleme, A. Dezerega, N. Silva, F.E. Gonzalez, R. Vernal, T. Sorsa, and J. Gamonal. 2011. Host-pathogen interactions in progressive chronic periodontitis. Journal of Dental Research 90 (10): 1164–1170. https://doi.org/10.1177/0022034511401405.
Sorsa, T., U.K. Gursoy, S. Nwhator, M. Hernandez, T. Tervahartiala, J. Leppilahti, M. Gursoy, E. Könönen, G. Emingil, P.J. Pussinen, and P. Mäntylä. 2016. Analysis of matrix metalloproteinases, especially MMP-8, in gingival creviclular fluid, mouthrinse and saliva for monitoring periodontal diseases. Periodontology 2000 70 (1): 142–163. https://doi.org/10.1111/prd.12101.
Makela, M., T. Salo, V.J. Uitto, and H. Larjava. 1994. Matrix metalloproteinases (MMP-2 and MMP-9) of the oral cavity: cellular origin and relationship to periodontal status. Journal of Dental Research 73 (8): 1397–1406. https://doi.org/10.1177/00220345940730080201.
Rai, B., S. Kharb, R. Jain, and S.C. Anand. 2008. Biomarkers of periodontitis in oral fluids. Journal of Oral Science 50 (1): 53–56.
Kubota, T., M. Itagaki, C. Hoshino, M. Nagata, T. Morozumi, T. Kobayashi, R. Takagi, and H. Yoshie. 2008. Altered gene expression levels of matrix metalloproteinases and their inhibitors in periodontitis-affected gingival tissue. Journal of Periodontology 79 (1): 166–173. https://doi.org/10.1902/jop.2008.070159.
Kusano, K., C. Miyaura, M. Inada, T. Tamura, A. Ito, H. Nagase, K. Kamoi, and T. Suda. 1998. Regulation of matrix metalloproteinases (MMP-2, −3, −9, and −13) by interleukin-1 and interleukin-6 in mouse calvaria: association of MMP induction with bone resorption. Endocrinology 139 (3): 1338–1345. https://doi.org/10.1210/endo.139.3.5818.
Shi, J., E. Schmitt-Talbot, D.A. DiMattia, and R.G. Dullea. 2004. The differential effects of IL-1 and TNF-alpha on proinflammatory cytokine and matrix metalloproteinase expression in human chondrosarcoma cells. Inflammation Research 53 (8): 377–389. https://doi.org/10.1007/s00011-004-1271-3.
Fujisaki, K., N. Tanabe, N. Suzuki, T. Kawato, O. Takeichi, O. Tsuzukibashi, M. Makimura, K. Ito, and M. Maeno. 2007. Receptor activator of NF-kappaB ligand induces the expression of carbonic anhydrase II, cathepsin K, and matrix metalloproteinase-9 in osteoclast precursor RAW264.7 cells. Life Sciences 80 (14): 1311–1318. https://doi.org/10.1016/j.lfs.2006.12.037.
Suh, S.J., C.H. Kwak, K.H. Song, K.M. Kwon, T.W. Chung, S.H. Cho, Y.K. Kim, et al. 2012. Triple inhibitory activity of Cliona celata against TNF-alpha-induced matrix metalloproteinase-9 production via downregulated NF-kappaB and AP-1, enzyme activity, and migration potential. Inflammation 35 (2): 736–745. https://doi.org/10.1007/s10753-011-9369-6.
Guan, S.M., L. Shu, S.M. Fu, B. Liu, X.L. Xu, and J.Z. Wu. 2008. Prevotella intermedia induces matrix metalloproteinase-9 expression in human periodontal ligament cells. FEMS Microbiology Letters 283 (1): 47–53. https://doi.org/10.1111/j.1574-6968.2008.01140.x.
Sanchavanakit, N., W. Saengtong, J. Manokawinchoke, and P. Pavasant. 2015. TNF-alpha stimulates MMP-3 production via PGE2 signalling through the NF-kB and p38 MAPK pathway in a murine cementoblast cell line. Archives of Oral Biology 60 (7): 1066–1074. https://doi.org/10.1016/j.archoralbio.2015.04.001.
Wang, Y.L., H. He, Z.J. Liu, Z.G. Cao, X.Y. Wang, K. Yang, Y. Fang, M. Han, C. Zhang, and F.Y. Huo. 2015. Effects of TNF-alpha on Cementoblast differentiation, mineralization, and apoptosis. Journal of Dental Research 94 (9): 1225–1232. https://doi.org/10.1177/0022034515590349.
Heussen, C., and E.B. Dowdle. 1980. Electrophoretic analysis of plasminogen activators in polyacrylamide gels containing sodium dodecyl sulfate and copolymerized substrates. Analytical Biochemistry 102 (1): 196–202.
Nakagawa, H., and K. Sakata. 1986. Partial purification and characterization of exudate gelatinase in the acute phase of carrageenin-induced inflammation in rats. Journal of Biochemistry 100 (6): 1499–1506.
Livak, K.J., and T.D. Schmittgen. 2001. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods 25 (4): 402–408. https://doi.org/10.1006/meth.2001.1262.
Lin, H.Y., B.R. Wells, R.E. Taylor, and H. Birkedal-Hansen. 1987. Degradation of type I collagen by rat mucosal keratinocytes. Evidence for secretion of a specific epithelial collagenase. The Journal of Biological Chemistry 262 (14): 6823–6831.
Ganguly, K., E. Rejmak, M. Mikosz, E. Nikolaev, E. Knapska, and L. Kaczmarek. 2013. Matrix metalloproteinase (MMP) 9 transcription in mouse brain induced by fear learning. The Journal of Biological Chemistry 288 (29): 20978–20991. https://doi.org/10.1074/jbc.M113.457903.
Martin, G., P. Bogdanowicz, F. Domagala, H. Ficheux, and J.P. Pujol. 2003. Rhein inhibits interleukin-1 beta-induced activation of MEK/ERK pathway and DNA binding of NF-kappa B and AP-1 in chondrocytes cultured in hypoxia: a potential mechanism for its disease-modifying effect in osteoarthritis. Inflammation 27 (4): 233–246.
Van den Steen, P.E., B. Dubois, I. Nelissen, P.M. Rudd, R.A. Dwek, and G. Opdenakker. 2002. Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Critical Reviews in Biochemistry and Molecular Biology 37 (6): 375–536. https://doi.org/10.1080/10409230290771546.
Liang, K.C., C.W. Lee, W.N. Lin, C.C. Lin, C.B. Wu, S.F. Luo, and C.M. Yang. 2007. Interleukin-1beta induces MMP-9 expression via p42/p44 MAPK, p38 MAPK, JNK, and nuclear factor-kappaB signaling pathways in human tracheal smooth muscle cells. Journal of Cellular Physiology 211 (3): 759–770. https://doi.org/10.1002/jcp.20992.
Wu, C.Y., H.L. Hsieh, C.C. Sun, C.P. Tseng, and C.M. Yang. 2008. IL-1 beta induces proMMP-9 expression via c-Src-dependent PDGFR/PI3K/Akt/p300 cascade in rat brain astrocytes. Journal of Neurochemistry 105 (4): 1499–1512. https://doi.org/10.1111/j.1471-4159.2008.05318.x.
Lin, C.C., C.T. Kuo, C.Y. Cheng, C.Y. Wu, C.W. Lee, H.L. Hsieh, I.T. Lee, and C.M. Yang. 2009. IL-1 beta promotes A549 cell migration via MAPKs/AP-1- and NF-kappaB-dependent matrix metalloproteinase-9 expression. Cellular Signalling 21 (11): 1652–1662. https://doi.org/10.1016/j.cellsig.2009.07.002.
Yasumitsu, H., K. Miyazaki, F. Umenishi, N. Koshikawa, and M. Umeda. 1992. Comparison of extracellular matrix-degrading activities between 64-kDa and 90-kDa gelatinases purified in inhibitor-free forms from human schwannoma cells. Journal of Biochemistry 111 (1): 74–80.
Aimes, R.T., and J.P. Quigley. 1995. Matrix metalloproteinase-2 is an interstitial collagenase. Inhibitor-free enzyme catalyzes the cleavage of collagen fibrils and soluble native type I collagen generating the specific 3/4- and 1/4-length fragments. The Journal of Biological Chemistry 270 (11): 5872–5876.
Patterson, M.L., S.J. Atkinson, V. Knauper, and G. Murphy. 2001. Specific collagenolysis by gelatinase a, MMP-2, is determined by the hemopexin domain and not the fibronectin-like domain. FEBS Letters 503 (2–3): 158–162.
Yan, C., and D.D. Boyd. 2007. Regulation of matrix metalloproteinase gene expression. Journal of Cellular Physiology 211 (1): 19–26. https://doi.org/10.1002/jcp.20948.
Huhtala, P., L.T. Chow, and K. Tryggvason. 1990. Structure of the human type IV collagenase gene. The Journal of Biological Chemistry 265 (19): 11077–11082.
Huhtala, P., L. Chow, T. Shows, and K. Tryggvason. 1992. Structure of the human 70 K type IV collagenase gene and assignment of the gene to the q21 region of chromosome 16. Matrix Supplement 1: 84.
Tseng, H.C., I.T. Lee, C.C. Lin, P.L. Chi, S.E. Cheng, R.H. Shih, L.D. Hsiao, and C.M. Yang. 2013. IL-1beta promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-kappaB- and AP-1-dependent pathways. PLoS One 8 (3): e57955. https://doi.org/10.1371/journal.pone.0057955.
Cargnello, M., and P.P. Roux. 2011. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases. Microbiology and Molecular Biology Reviews 75 (1): 50–83. https://doi.org/10.1128/mmbr.00031-10.
Wu, C.Y., H.L. Hsieh, M.J. Jou, and C.M. Yang. 2004. Involvement of p42/p44 MAPK, p38 MAPK, JNK and nuclear factor-kappa B in interleukin-1beta-induced matrix metalloproteinase-9 expression in rat brain astrocytes. Journal of Neurochemistry 90 (6): 1477–1488. https://doi.org/10.1111/j.1471-4159.2004.02682.x.
Huang, Q., F. Lan, X. Wang, Y. Yu, X. Ouyang, F. Zheng, J. Han, Y. Lin, Y. Xie, F. Xie, W. Liu, X. Yang, H. Wang, L. Dong, L. Wang, and J. Tan. 2014. IL-1beta-induced activation of p38 promotes metastasis in gastric adenocarcinoma via upregulation of AP-1/c-fos, MMP2 and MMP9. Molecular Cancer 13: 18. https://doi.org/10.1186/1476-4598-13-18.
Karin, M. 1996. The regulation of AP-1 activity by mitogen-activated protein kinases. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 351 (1336): 127–134. https://doi.org/10.1098/rstb.1996.0008.
Van den Steen, P.E., P. Proost, D.D. Brand, A.H. Kang, J. Van Damme, and G. Opdenakker. 2004. Generation of glycosylated remnant epitopes from human collagen type II by gelatinase B. Biochemistry 43 (33): 10809–10816. https://doi.org/10.1021/bi0493665.
Havemose-Poulsen, A., P. Holmstrup, K. Stoltze, and H. Birkedal-Hansen. 1998. Dissolution of type I collagen fibrils by gingival fibroblasts isolated from patients of various periodontitis categories. Journal of Periodontal Research 33 (5): 280–291.
Tsai, C.L., W.C. Chen, I.T. Lee, P.L. Chi, S.E. Cheng, and C.M. Yang. 2014. C-Src-dependent transactivation of PDGFR contributes to TNF-alpha-induced MMP-9 expression and functional impairment in osteoblasts. Bone 60: 186–197. https://doi.org/10.1016/j.bone.2013.12.014.
Zijlstra, A., R.T. Aimes, D. Zhu, K. Regazzoni, T. Kupriyanova, M. Seandel, E.I. Deryugina, and J.P. Quigley. 2004. Collagenolysis-dependent angiogenesis mediated by matrix metalloproteinase-13 (collagenase-3). The Journal of Biological Chemistry 279 (26): 27633–27645. https://doi.org/10.1074/jbc.M313617200.
Hu, J., P.E. Van den Steen, Q.X. Sang, and G. Opdenakker. 2007. Matrix metalloproteinase inhibitors as therapy for inflammatory and vascular diseases. Nature Reviews. Drug Discovery 6 (6): 480–498. https://doi.org/10.1038/nrd2308.
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This study was financially supported by grants from the National Natural Science Foundation of China (Nos. 81671020, 81200811, and 81701013).
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Mingyuan Du contributed to conception and design, contributed to data acquisition, analysis, and interpretation, and drafted the manuscript. Yunlong Wang, Zhingjian Liu, Leilei Wang, Zhengguo Cao contributed to conception and design; Chen Zhang and Hong He contributed to data analysis and interpretation; Yunlong Wang and Yunru Hao contributed to acquisition. All authors critically revised the manuscript, gave final approval, and agree to be accountable for all aspects of the work, ensuring integrity and accuracy.
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Du, M., Wang, Y., Liu, Z. et al. Effects of IL-1β on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen. Inflammation 42, 413–425 (2019). https://doi.org/10.1007/s10753-018-00951-6
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DOI: https://doi.org/10.1007/s10753-018-00951-6