Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice.
Plasmid encoding microRNA-200c ameliorates periodontitis and systemic inflammation in obese mice.
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DOI：
10.1016/j.omtn.2021.01.030
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发表时间：
2021-03-05
期刊：
影响因子：
--
通讯作者：
Hong L
中科院分区：
文献类型：
--
作者：
Krongbaramee T;Zhu M;Qian Q;Zhang Z;Eliason S;Shu Y;Qian F;Akkouch A;Su D;Amendt BA;Yang L;Hong L
本研究旨在表征microRNA-200c （miR-200c）及其调控因子在肥胖受试者（pios）的脂肪生成分化、肥胖和牙周炎中的作用，并确定编码miR-200c的质粒DNA治疗pios的疗效。我们报道，在饮食诱导的肥胖（DIO）小鼠和人骨髓间充质间质细胞（hBMSCs）的成脂分化过程中，牙龈组织中高表达的miR-200c被下调。在DIO小鼠的上颌牙间龈局部注射牙龈卟啉单胞菌脂多糖（Pg-LPS）可降低牙龈和脂肪组织中的miR-200c，诱导牙周炎症，并伴有全身白细胞介素-6 （IL-6）升高和糖耐量受损。体外实验证实了Pg-LPS和IL-6对miR-200c的抑制作用及其对Zeb1的抑制作用。将编码miR-200c的裸质粒DNA注射到牙龈中，有效地挽救了miR-200c的下调，预防了牙周和全身炎症，减轻了脂多糖诱导的肥胖小鼠牙周炎的糖代谢障碍。循环外泌体miR-200c的增加及其抑制促炎细胞因子和脂肪生成的功能解释了miR-200c在PiOSs中减轻全身炎症的牙龈应用机制。这些结果表明，在牙周炎和肥胖中，通过Pg-LPS和IL-6降低miR-200c可能导致pios的发病机制，而在牙龈中上调miR-200c为pios的治疗提供了一种途径。肥胖小鼠牙周炎下调miR-200c，增加全身炎症，损害糖耐量。在牙龈中过表达miR-200c可减轻牙周炎、全身炎症和葡萄糖耐受不良。miR-200c与脂肪生成、炎症和破骨细胞生成的相互作用表明其在肥胖受试者牙周炎发病和治疗中的作用。
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. 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.
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