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EZH2 Promotes Extracellular Matrix Degradation via Nuclear Factor-κB (NF-κB) and p38 Signaling Pathways in Pulpitis

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Abstract

Pulpitis is a complicated chronic inflammatory process which can be in a dynamic balance between damage and repair. The extracellular matrix plays an important regulatory role in wound healing and tissue repair. The aim of this study was to explore the role of the epigenetic mark, enhancer of zeste homolog 2 (EZH2) on the degradation of extracellular matrix during pulpitis. Quantitative polymerase chain reaction was used to assess the expression of matrix metalloproteinases (MMPs) and type I collagen in human dental pulp cells (HDPCs) upon EZH2 and EI1 (EZH2 inhibitor) stimulation. The mechanism of EZH2 affecting extracellular matrix was explored through quantitative polymerase chain reaction and Western blot. A rat model of dental pulp inflammation was established, and the expression of type I collagen in dental pulp under EZH2 stimulation was detected by immunohistochemical staining. EZH2 upregulated the expression of MMP-1, MMP-3, MMP-8, and MMP-10 and decreased the production of type I collagen in HDPCs, while EI1 had the opposite effect. EZH2 activated the nuclear factor-kappa B (NF-κB) and p38 signaling pathways in HDPCs, the inhibition of which reversed the induction of MMPs and the suppression of type I collagen. EZH2 can downregulate the type I collagen levels in an experimental model of dental pulpitis in rats. EZH2 promotes extracellular matrix degradation via nuclear factor-κB (NF-κB) and P38 signaling pathways in pulpitis. EZH2 can decrease the type I collagen levels in vivo and in vitro.

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Data Availability

All data generated or analyzed during this study are included in this published article.

Abbreviations

CK:

Cytokeratins

ECM:

Extracellular matrix

HDPC:

Human dental pulp cell

JMJD3:

Jumonji domain protein 3

MMPs:

Matrix metalloproteinases

MAPK:

Mitogen-activated protein kinase

NF-κB:

Nuclear factor-κB

q-PCR:

Quantitative polymerase chain reaction

EZH2:

Zeste homolog 2

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Funding

This work was supported by the Natural Science Foundation of China (NSFC) (grant # 81800959).

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Authors and Affiliations

  1. Department of Pediatric Dentistry, Central Laboratory, Peking University School and Hospital of Stomatology & National Center of Stomatology &National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, No.22, Zhongguancun South Avenue, Haidian District, Beijing, 100081, PR, China

    Jie He, Man Qin, Yingyi Chen, Ziqi Hu & Tianqian Hui

  2. State Key Laboratory of Oral Diseases, West China Hospital of Stomatology, Sichuan University, Sichuan, China

    Ling Ye

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  1. Jie He
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Contributions

Jie He, Tianqian Hui, and Man Qin designed the study; Jie He and Yingyi Chen performed the research. Jie He, Yingyi Chen, and Ziqi Hu analyzed the data and contributed to the search and collation of literature. Jie He and Ling Ye wrote the manuscript. Ling Ye, Man Qin, and Tianqian Hui contributed to the revision of the manuscript.

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Correspondence to Man Qin or Tianqian Hui.

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Ethics approval and consent to participate

The entire study was approved by the human research committee of Peking University School of Stomatology (ethics approval number: PKUSSIRB-201732003) and performed after written informed consent from patients was obtained. This study has been verified by the Peking University Biomedical Ethics Committee Approved by the Animal Welfare Ethics Committee (Approval Number: LA2018044).

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The authors declare no competing interests.

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He, J., Qin, M., Chen, Y. et al. EZH2 Promotes Extracellular Matrix Degradation via Nuclear Factor-κB (NF-κB) and p38 Signaling Pathways in Pulpitis. Inflammation 44, 1927–1936 (2021). https://doi.org/10.1007/s10753-021-01470-7

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  • DOI: https://doi.org/10.1007/s10753-021-01470-7

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