Effects of IL-1β on MMP-9 Expression in Cementoblast-Derived Cell Line and MMP-Mediated Degradation of Type I Collagen
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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.
KEY WORDSinterleukin-1β MAPK signaling pathway dental cementum matrix metalloproteinases cell-mediated collagen degradation
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.
This study was financially supported by grants from the National Natural Science Foundation of China (Nos. 81671020, 81200811, and 81701013).
Compliance with Ethical Standards
Conflict of Interest
The authors declare that they have no conflict of interest.
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