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Local Inflammation Alters MMP-2 and MMP-9 Gelatinase Expression Associated with the Severity of Nifedipine-Induced Gingival Overgrowth: a Rat Model Study

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Abstract

Nifedipine-induced gingival overgrowth (NIGO) is characterized by cell proliferation and extracellular matrix (ECM) component accumulation in gingival connective tissues, with varying degrees of inflammation and fibrosis. Impaired collagen and ECM homeostasis may be among the underlying molecular mechanisms that lead to the fibrotic changes that occur in drug-induced gingival overgrowth (DIGO). Because matrix metalloproteinases (MMPs) play vital roles in regulating collagen and ECM metabolism, many studies have been performed to reveal the relationship between MMPs and DIGO. It is thought that the gelatinases MMP-2 and MMP-9, both type IV collagenases, are involved in the development of tissue inflammation and organ fibrosis. However, the few studies regarding gelatinase expression in DIGO are controversial. Recent studies have demonstrated the inhibitory effect of cyclosporine A (CsA) on gelatinase expression and/or activity; however, similar changes have yet to be detected in Nif-treated gingival tissues. In this study, we verified that Nif treatment could lead to gingival overgrowth in rats and that gingival inflammation played a pro-proliferative role in NIGO development. Additionally, we examined the temporal expression of gelatinases on days 0, 7, 14, 21, 30, and 40 during NIGO development. The aim was to investigate whether MMP-2 and MMP-9 played significant roles in regulating NIGO development and progression. MMP-2 gene expression was not altered by Nif treatment alone but was significantly inhibited by Nif treatment for 30 days in the presence of local inflammation. However, no significant alterations in MMP-2 protein expression were detected in the Nif-treated gingival tissue, regardless of the presence or absence of local inflammation. Moreover, Nif treatment could lead to transient and significant increases in MMP-9 gene and protein expression levels in the presence of local inflammation. In particular, active MMP-9 expression increased significantly in the gingival tissue that received the combined effect of Nif and ligation treatment; besides, a temporal, but not significant, change was also observed in the gingival tissue that received Nif treatment alone. Taken together, these results provided evidence that temporal changes in MMP-2 and MMP-9 expression occurred during NIGO development. Nif treatment accompanied by local inflammation regulated MMP-2 and MMP-9 expression, primarily MMP-9, which was most likely associated with NIGO severity. Thus, MMP-9 is a potential contributing factor in the process of NIGO development.

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Acknowledgments

We are very grateful for the assistance from Yi Eve Sun’s Lab at the Translational Center for Stem Cell Research, Tongji Hospital, Tongji University School of Medicine. We thank Prof. Yi Eve Sun for her guidance in our research work and Dr. Bo Jing for her technical support. This work was supported by National Natural Science Foundation of China (No.81070825, 81170951).

Conflicts of Interest

The authors deny any conflicts of interest related to this study.

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Authors and Affiliations

  1. Department of Conservative Dentistry, Laboratory of Oral Biomedical Science and Translational Medicine, School of Stomatology, Tongji University, Shanghai, 200072, People’s Republic of China

    Wu-Li Li, Cheng-Hai Wu, Jun Yang, Min Tang, Long-Jie Chen & Shou-Liang Zhao

  2. Department of Operative Dentistry and Endodontic, Key Laboratory of Oral Diseases Research of Anhui Province, Stomatologic Hospital and College, Anhui Medical University, Hefei, 230032, China

    Wu-Li Li

  3. Department of Stomatology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, 200040, People’s Republic of China

    Shou-Liang Zhao

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Correspondence to Shou-Liang Zhao.

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Li, WL., Wu, CH., Yang, J. et al. Local Inflammation Alters MMP-2 and MMP-9 Gelatinase Expression Associated with the Severity of Nifedipine-Induced Gingival Overgrowth: a Rat Model Study. Inflammation 38, 1517–1528 (2015). https://doi.org/10.1007/s10753-015-0126-0

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