Journal article
Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice
Molecular therapy. Nucleic acids, Vol.23, pp.1204-1216
03/05/2021
DOI: 10.1016/j.omtn.2021.01.030
PMCID: PMC7899952
PMID: 33664998
Abstract
The present study was conducted to characterize microRNA-200c (miR-200c) and its regulators in adipogenic differentiation, obesity, and periodontitis in obese subjects (PiOSs), and to determine the therapeutic efficacy of plasmid DNA encoding miR-200c as a treatment for PiOSs. We report that highly expressed miR-200c in gingival tissues was downregulated in diet-induced obese (DIO) mice and during adipogenic differentiation of human bone marrow mesenchymal stromal cells (hBMSCs). Local injection of Porphyromonas gingivalis lipopolysaccharide (Pg-LPS) in the maxilla interdental gingiva of DIO mice reduced miR-200c in gingival and adipose tissues and induced periodontal inflammation associated with systemic elevation of interleukin-6 (IL-6) and impaired glucose tolerance. The inhibitory functions of Pg-LPS and IL-6 on miR-200c and their effectiveness on Zeb1 were confirmed in vitro. Injection of naked plasmid DNA encoding miR-200c into the gingiva effectively rescued miR-200c downregulation, prevented periodontal and systemic inflammation, and alleviated the impaired glucose metabolism in obese mice with LPS-induced periodontitis. Increased circulating exosomal miR-200c and its function on suppressing proinflammatory cytokines and adipogenesis explained the mechanism(s) of gingival application of miR-200c in attenuating systemic inflammation in PiOSs. These results demonstrated that miR-200c reduced by Pg-LPS and IL-6 in periodontitis and obesity might lead to the pathogenesis of PiOSs, and upregulation of miR-200c in the gingiva presents a therapeutic approach for PiOSs.
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Periodontitis in obese mice downregulates miR-200c, increases systemic inflammation, and impairs glucose tolerance. miR-200c overexpression in the gingiva attenuates the periodontitis and the systemic inflammation and glucose intolerance. The interactions of miR-200c with adipogenesis, inflammation, and osteoclastogenesis indicate its roles in the pathogenesis and treatment of periodontitis in obese subjects.
Details
- Title: Subtitle
- Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice
- Creators
- Tadkamol Krongbaramee - University of IowaMin Zhu - University of IowaQingwen Qian - University of IowaZeyuan Zhang - University of IowaSteven Eliason - University of IowaYi Shu - University of IowaFang Qian - University of IowaAdil Akkouch - University of IowaDan Su - University of IowaBrad A. Amendt - University of IowaLing Yang - University of IowaLiu Hong - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular therapy. Nucleic acids, Vol.23, pp.1204-1216
- DOI
- 10.1016/j.omtn.2021.01.030
- PMID
- 33664998
- PMCID
- PMC7899952
- NLM abbreviation
- Mol Ther Nucleic Acids
- ISSN
- 2162-2531
- eISSN
- 2162-2531
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000072, name: National Institute of Dental and Craniofacial Research
- Language
- English
- Date published
- 03/05/2021
- Academic Unit
- Preventive and Community Dentistry; Roy J. Carver Department of Biomedical Engineering; Orthodontics; Molecular Physiology and Biophysics; Anatomy and Cell Biology; Prosthodontics; Craniofacial Anomalies Research Center; Fraternal Order of Eagles Diabetes Research Center; Dental Research
- Record Identifier
- 9984284454702771
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