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CTHRC1 Knockdown Promotes Inflammatory Responses Partially by p38 MAPK Activation in Human Periodontal Ligament Cells

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Abstract

Collagen triple helix repeat containing 1 (CTHRC1), a secreted glycoprotein, is widely expressed in many tissues. It has been recently defined as a novel marker for rheumatoid arthritis (RA), a systemic inflammatory disorder. However, the precise role of CTHRC1 in other chronic inflammatory diseases, like periodontal disease, remains unclear. This research aimed to explore the presence of CTHRC1 in periodontal inflammation, determine the precise role in inflammatory response modulation in periodontal ligament cells (PDLCs), and explore its underlying mechanisms. In vivo gingival crevicular fluid (GCF) and gingivae were obtained from healthy people and chronic periodontitis patients. Maxillary tissues of mice with or without ligature-induced periodontitis were immunostained for CTHRC1. In vitro human PDLCs were treated with tumor necrosis factor alpha (TNF-α) to mimic the inflammatory environment. Small interfering RNA (siRNA) was used to silence CTHRC1. SB203580 was used to inhibit the p38 mitogen-activated protein kinase (MAPK) pathway. CTHRC1 was highly expressed in GCF and gingival tissues of periodontitis patients. Animal models also revealed the same tendency. CTHRC1 knockdown promoted inflammatory cytokine production and activated the p38 MAPK signaling pathway in PDLCs. Inhibiting the p38 MAPK signaling pathway partially attenuated the inflammatory responses. This study revealed that CTHRC1 was highly expressed in periodontitis and suggested that CTHRC1 might play an important role in modulating periodontal inflammation.

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Data availability

The datasets used or analyzed during the current study are available from the corresponding author on reasonable request.

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Funding

The study was supported by grants from the National Natural Science Foundation of China to Zhengguo Cao (81870776 and 81570946).

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Authors and Affiliations

  1. The State Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST KLOS) & Key Laboratory of Oral Biomedicine Ministry of Education (KLOBME), School & Hospital of Stomatology, Wuhan University, Wuhan, China

    Yi Guo, Chenxi Jiang, Siqi Yao, Li Ma, Huihui Zhang, Xiaoxuan Wang, Shihan Xu & Zhengguo Cao

  2. Department of Periodontology, School & Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Hongshan District, Wuhan, 430079, China

    Huihui Zhang, Xiaoxuan Wang & Zhengguo Cao

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  1. Yi Guo
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  2. Chenxi Jiang
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  4. Li Ma
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  8. Zhengguo Cao
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Contributions

YG contributed to conception, design, data acquisition, analysis, and interpretation, drafted and critically revised the manuscript; CJ, SY, LM contributed to design, data acquisition, and analysis, critically revised the manuscript; HZ, XW, SX contributed to data acquisition and analysis, critically revised the manuscript; ZC contributed to conception, design, and interpretation, drafted and critically revised the manuscript.

Corresponding author

Correspondence to Zhengguo Cao.

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Ethics approval and consent to participate

The animal study was performed in accordance with the care and use of the laboratory animal manual by the US National Institutes of Health. This clinical study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of the Wuhan University School of Stomatology (authorized c-14/2014). Informed consent was obtained from all individual participants included in the study.

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The authors declare no competing interests.

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Guo, Y., Jiang, C., Yao, S. et al. CTHRC1 Knockdown Promotes Inflammatory Responses Partially by p38 MAPK Activation in Human Periodontal Ligament Cells. Inflammation 44, 1831–1842 (2021). https://doi.org/10.1007/s10753-021-01461-8

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