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Loss of Dec1 prevents autophagy in inflamed periodontal ligament fibroblast

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Abstract

Periodontal ligament fibroblasts (PDLFs) are integral to the homeostasis of periodontal tissue. The transcription factor Dec1 functions to modulate Porphyromonas gingivalis-induced periodontal inflammation. Here, we aimed to characterize the Dec1-mediated autophagy in PDLFs under inflammatory conditions. Human PDLFs were subjected to an inflammatory environment using P. gingivalis Lipopolysaccaride (LPS) along with Dec1 siRNA in vitro. Quantitative real-time polymerase chain reaction and Western blot analyses were used to evaluate the expression levels of autophagy-related genes and their upstream AKT/mTOR signaling pathways. An experimental P. gingivalis-treated Dec1 knockout (Dec1KO) mouse model was used to confirm the expression of autophagy in PDLFs in vivo. Treatment with P. gingivalis LPS induced the expression of ATG5, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3) and elevated the expression of pro-inflammatory cytokine IL-1β and Dec1 in human PDLFs. Knockdown of Dec1 partly reversed the detrimental influences of LPS on these autophagy markers in human PDLFs. The inhibition of autophagy with Dec1 siRNA suppressed the inflammatory effect of AKT/mTOR signaling pathways following treatment with P. gingivalis LPS. P. gingivalis-treated Dec1KO mice partly reduced autophagy expression. These findings suggest that a Dec1 deficiency can modulate the interaction between autophagy and inflammation in PDLFs.

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Data availability

The datasets used and analyzed in this study are available from the corresponding author (chocolate_yan@yeah.net) on reasonable request.

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Acknowledgements

We would like to thank Professor Yukio Kato for providing Dec1KO mice, Dr. Toyama and Dr. Sato for the P. gingivalis treatment and the staff of the animal facility for care of the mice. We thank Dr. Fujita for technical assistance.

Funding

This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan and by a Nihon University Multidisciplinary Research Grant for 2018.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, Nihon University School of Dentistry, Tokyo, Japan

    Shunichi Oka & Yoshiyuki Oi

  2. Division of Immunology and Pathology, Dental Research Center, Nihon University School of Dentistry, Tokyo, Japan

    Shunichi Oka & Yoshiyuki Oi

  3. Laboratory of Tissue Regeneration and Immunology and Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Beijing, People’s Republic of China

    Xiaoyan Li & Yi Liu

  4. Department of Anesthesiology, Nihon University School of Dentistry At Matsudo, Chiba, Japan

    Fengzhu Zhang

  5. Division of Pedodontics and Preventive Dentistry, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India

    Nitesh Tewari

  6. Department of Dental Hygiene, Honam University, Gwangju, Republic of Korea

    Il-Shin Kim

  7. Department of Stomatology, Hangzhou Normal University, Hangzhou, People’s Republic of China

    Chongchong Chen & Liangjun Zhong

  8. Division of Microbiology, Department of Oral Science, Graduate School of Dentistry, Kanagawa Dental University, Yokosuka, Japan

    Nobushiro Hamada

  9. Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Tokyo, Japan

    Makoto Makishima

  10. Department of Biochemistry and Molecular Biology, Nihon University School of Dentistry At Matsudo, Chiba, Japan

    Ujjal K. Bhawal

Authors
  1. Shunichi Oka
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  2. Xiaoyan Li
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  12. Ujjal K. Bhawal
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Contributions

SO, XL, FZ and UKB performed the experiments, XL and UKB wrote the manuscript. SO, XL, FZ and UKB conceived the study and analyzed the data. FZ, NH, YO and UKB designed the animal experiments. NT, ISK, CC, LZ, MM and YL supervised interpretation of the data and critical review of the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiaoyan Li or Ujjal K. Bhawal.

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The authors have no conflict of interest to declare.

Ethical approval

All procedures were performed in compliance with the standard principles and guidelines for the care and use of laboratory animals of Animal Ethics Committee of Kanagawa Dental University (Approval No. 12–042).

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11033_2021_6162_MOESM1_ESM.tif

Fig. S1 Expression of hypoxia and ROS related proteins was also decreased in Dec1 KO mice compared to WT mice (TIF 23213 KB)

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Oka, S., Li, X., Zhang, F. et al. Loss of Dec1 prevents autophagy in inflamed periodontal ligament fibroblast. Mol Biol Rep 48, 1423–1431 (2021). https://doi.org/10.1007/s11033-021-06162-x

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  • DOI: https://doi.org/10.1007/s11033-021-06162-x

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