Leptin-deficient ob/ob mice exhibit periodontitis phenotype and altered oral microbiome

Zhicong Li, Zhichao Zheng, Janak L. Pathak, Hongtao Li, Gang Wu, Shaofen Xu, Tianqi Wang, Haoyu Cheng, Zhengguo Piao*, Richard T. Jaspers, Lihong Wu

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Background and Objective: Leptin-deficient obesity is associated with various systemic diseases including diabetes and low bone mass phenotype. However, the periodontal status of leptin-deficient obese individuals is still unclear. In this study, we aimed to analyze the periodontal status, alveolar bone phenotype, and oral microbiome status in leptin-deficient obese mice (ob/ob mice). Methods: This study used 12-week-old wild-type and ob/ob male mice. The alveolar bone phenotype and periodontal status in the maxilla were analyzed by micro-CT and histological analysis. Osteoclasts in alveolar bone were visualized by TRAP staining. Expressions of inflammatory markers (MMP-9, IL-1β, and TGF-β1) and osteoclastogenic markers (RANKL and OPG) in periodontium were analyzed by immunohistochemistry and RT-qPCR. The oral microbiome was analyzed by 16 S rDNA sequencing. Results: CEJ-ABC distance in maxillary molars (M1-M3) of ob/ob mice was significantly higher compared with that of wild-type. The alveolar bone BV/TV ratio was reduced in ob/ob mice compared with wild-type. Higher numbers of osteoclasts were observed in ob/ob mice alveolar bone adjacent to the molar root. Epithelial hyperplasia in gingiva and disordered periodontal ligaments was observed in ob/ob mice. RANKL/OPG expression ratio was increased in ob/ob mice compared with wild-type. Expressions of inflammatory markers MMP-9, IL-1β, and TGF-β1 were increased in ob/ob mice compared with wild-type. Oral microbiome analysis showed that beneficial bacteria Akkermansia and Ruminococcaceae_UCG_014 were more abundant in the wild-type mice while the inflammation-related Flavobacterium was more abundant in ob/ob mice. Conclusion: In conclusion, ob/ob mice showed higher expressions of inflammatory factors, increased alveolar bone loss, lower abundance of the beneficial bacteria, and higher abundance of inflammatory bacteria in the oral cavity, suggesting leptin-deficient obesity as a risk factor for periodontitis development in ob/ob mice.

Original languageEnglish
Pages (from-to)392-402
Number of pages11
JournalJournal of Periodontal Research
Volume58
Issue number2
Early online date29 Jan 2023
DOIs
Publication statusPublished - Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Journal of Periodontal Research published by John Wiley & Sons Ltd.

Funding

The present study was supported by the National Natural Science Foundation of China (U22A20159, 82150410451), Science and Technology program of Guangzhou (202201010073, 202201020116), General Guiding Project of Guangzhou (20201A011105), Medical Scientific Research Foundation of Guangdong Province (B2020027).

FundersFunder number
General Guiding Project of Guangzhou20201A011105
National Natural Science Foundation of ChinaU22A20159, 82150410451
Guangdong Medical Research FoundationB2020027
Guangzhou Science and Technology Program key projects202201020116, 202201010073

    Keywords

    • leptin
    • microbiome
    • ob/ob mice
    • periodontitis

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