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. 2021 Aug;56(4):667-678.
doi: 10.1111/jre.12863. Epub 2021 Mar 2.

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation

Peng Zhang  1   2 , Boyao Lu  1   2 , Rui Zhu  1   2 , Dawei Yang  1   2 , Weiqing Liu  1   2 , Qian Wang  1   2 , Ning Ji  1 , Qianming Chen  1 , Yi Ding  1   3 , Xing Liang  1   2 , Qi Wang  1   2
Affiliations

Hyperglycemia accelerates inflammaging in the gingival epithelium through inflammasomes activation

Peng Zhang et al. J Periodontal Res. 2021 Aug.

Abstract

Background and objective: Diabetes accelerates inflammaging in various tissue with an increase in senescent cell burden and senescence-associated secretory phenotype (SASP) secretion, which is a significant cause of tissue dysfunction and contributes to the diabetic complications. Recently, inflammasomes are thought to contribute to inflammaging. Here, utilizing diabetic models in vivo and in vitro, we investigated the potential association between hyperglycemia-induced inflammaging and gingival tissue dysfunction and the mechanism underlying inflammasome-associated inflammaging.

Materials and methods: Gingival epithelium and serum were collected from control and diabetic patients and mice. The expression of p16, p21, and inflammasomes in the gingival epithelium, SASP factors in serum, and the molecular factors associated with gingival epithelial barrier function were assessed. Human oral keratinocyte (HOK) was stimulated with normal and high glucose, and pre-treated with Z-YVAD-FMK (Caspase-1 inhibitor) prior to evaluating cellular senescence, SASP secretion, and inflammasome activation.

Results: In vivo, hyperglycemia significantly elevated the local burden of senescent cells in the gingival epithelium and SASP factors in the serum and simultaneously reduced the expression levels of Claudin-1, E-cadherin, and Connexin 43 in the gingival epithelium. Interestingly, the inflammasomes were activated in the gingival epithelium. In vitro, high glucose-induced the inflammaging in HOK, and blocking inflammasome activation through inhibiting Caspase-1 and glucose-induced inflammaging.

Conclusions: Hyperglycemia accelerated inflammaging in the gingival epithelium through inflammasomes activation, which is potentially affiliated with a decline in the gingival epithelial barrier function in diabetes. Inflammasomes-related inflammaging may be the crucial mechanism underlying diabetic periodontitis and represents significant opportunities for advancing prevention and treatment options.

Keywords: diabetes; gingival epithelium; inflammaging; inflammasome.

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References

REFERENCES

    1. Nolan CJ, Damm P, Prentki M. Type 2 diabetes across generations: from pathophysiology to prevention and management. Lancet. 2011;378(9786):169-181.
    1. Lalla E, Papapanou PN. Diabetes mellitus and periodontitis: a tale of two common interrelated diseases. Nat Rev Endocrinol. 2011;7(12):738-748.
    1. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: Framework and proposal of a new classification and case definition. J Periodontol. 2018;89(Suppl 1):S159-S172.
    1. Jepsen S, Caton JG, Albandar JM, et al. Periodontal manifestations of systemic diseases and developmental and acquired conditions: Consensus report of workgroup 3 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Clin Periodontol. 2018;45(Suppl 20):S219-S229.
    1. Perkisas S, Vandewoude M. Where frailty meets diabetes. Diabetes Metab Res Rev. 2016;32(Suppl 1):261-267.

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