瘦素缺乏的ob/ob小鼠表现出牙周炎表型和口腔微生物群改变。
Leptin-deficient ob/ob mice exhibit periodontitis phenotype and altered oral microbiome.
作者信息
Li Zhicong, Zheng Zhichao, Pathak Janak L, Li Hongtao, Wu Gang, Xu Shaofen, Wang Tianqi, Cheng Haoyu, Piao Zhengguo, Jaspers Richard T, Wu Lihong
机构信息
Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, Guangdong, China.
Laboratory for Myology, Department of Human Movement Sciences, Faculty of Behavioural and Movement Sciences, Vrije Universiteit Amsterdam, Amsterdam Movement Sciences, Amsterdam, HZ, The Netherlands.
出版信息
J Periodontal Res. 2023 Apr;58(2):392-402. doi: 10.1111/jre.13099. Epub 2023 Jan 29.
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.
背景与目的
瘦素缺乏型肥胖与包括糖尿病和低骨量表型在内的多种全身性疾病相关。然而，瘦素缺乏型肥胖个体的牙周状况仍不清楚。在本研究中，我们旨在分析瘦素缺乏型肥胖小鼠（ob/ob小鼠）的牙周状况、牙槽骨表型和口腔微生物群状态。
方法
本研究使用12周龄的野生型和ob/ob雄性小鼠。通过显微CT和组织学分析对上颌的牙槽骨表型和牙周状况进行分析。通过抗酒石酸酸性磷酸酶（TRAP）染色观察牙槽骨中的破骨细胞。通过免疫组织化学和逆转录定量聚合酶链反应（RT-qPCR）分析牙周组织中炎症标志物（基质金属蛋白酶-9、白细胞介素-1β和转化生长因子-β1）和成骨细胞生成标志物（核因子κB受体活化因子配体和骨保护素）的表达。通过16S核糖体DNA测序分析口腔微生物群。
结果
与野生型相比，ob/ob小鼠上颌磨牙（M1-M3）的釉牙骨质界-牙槽嵴顶（CEJ-ABC）距离显著更高。与野生型相比，ob/ob小鼠的牙槽骨骨体积分数（BV/TV）降低。在ob/ob小鼠磨牙牙根相邻的牙槽骨中观察到更多的破骨细胞。在ob/ob小鼠中观察到牙龈上皮增生和牙周韧带紊乱。与野生型相比，ob/ob小鼠中核因子κB受体活化因子配体/骨保护素（RANKL/OPG）表达比值增加。与野生型相比，ob/ob小鼠中炎症标志物基质金属蛋白酶-9、白细胞介素-1β和转化生长因子-β1的表达增加。口腔微生物群分析表明，有益菌阿克曼氏菌和瘤胃球菌科_UCG_014在野生型小鼠中更为丰富，而与炎症相关的黄杆菌在ob/ob小鼠中更为丰富。
结论
总之，ob/ob小鼠表现出炎症因子表达更高、牙槽骨吸收增加、有益菌丰度降低以及口腔中炎症菌丰度更高，提示瘦素缺乏型肥胖是ob/ob小鼠发生牙周炎的一个危险因素。
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