Wu Zhicong, Zhao Li, Guo Yi, Lin Chuyin, Lu Peipei, He Qian, Zhou Yinghong, Wang Xinhong, Yu Ting
Department of Periodontics and Oral Medicine, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction and Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, China.
Department of Prosthodontics, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-Sen University and Guangdong Provincial Key Laboratory of Stomatology, Guangzhou, China.
J Clin Periodontol. 2025 May;52(5):773-786. doi: 10.1111/jcpe.14144. Epub 2025 Feb 20.
To investigate the effects of hyperuricemia on periodontitis and the underlying mechanisms by establishing combined animal and cell models.
A hyperuricemia mouse model was established by potassium oxonate injection, with sodium carboxymethylcellulose treatment serving as controls. Both models were treated with or without periodontitis induction (n = 10/group). RAW264.7 macrophages and THP-1-derived macrophages were stimulated with Porphyromonas gingivalis -lipopolysaccharide in the presence of normal or excessive concentrations of uric acid. Allopurinol intervention was applied to both animal and cell models. Periodontal destruction was measured by micro-computed tomography and histology. The immune response and oxidative stress in the periodontium and macrophages were assessed using various methods including immunohistochemistry, quantitative PCR, western blotting, flow cytometry and multiplex cytokine assays.
Potassium oxonate successfully induced hyperuricemia without affecting serum glucose/lipid levels or xanthine oxidoreductase activity. In mice with periodontitis, hyperuricemia exacerbated alveolar bone loss and the presence of osteoclasts and M1 macrophages. Mechanistically, hyperuricemia promoted NLRP3 inflammasome activation, disrupted the inflammatory cytokine response and exacerbated oxidative stress both in the periodontium and in vitro. Allopurinol treatment reversed all relevant changes in both mice and macrophages.
Hyperuricemia exacerbates periodontitis possibly via uric acid-induced periodontal inflammation and oxidative stress.
通过建立动物和细胞联合模型，研究高尿酸血症对牙周炎的影响及其潜在机制。
通过注射氧嗪酸钾建立高尿酸血症小鼠模型，以羧甲基纤维素钠处理作为对照。两种模型均进行或不进行牙周炎诱导（每组n = 10）。在正常或过量尿酸浓度存在的情况下，用牙龈卟啉单胞菌脂多糖刺激RAW264.7巨噬细胞和THP-1衍生的巨噬细胞。对动物和细胞模型均应用别嘌呤醇干预。通过显微计算机断层扫描和组织学测量牙周破坏情况。使用包括免疫组织化学、定量PCR、蛋白质印迹、流式细胞术和多重细胞因子检测等各种方法评估牙周组织和巨噬细胞中的免疫反应和氧化应激。
氧嗪酸钾成功诱导高尿酸血症，且不影响血清葡萄糖/脂质水平或黄嘌呤氧化还原酶活性。在患有牙周炎的小鼠中，高尿酸血症加剧了牙槽骨丢失以及破骨细胞和M1巨噬细胞的存在。机制上，高尿酸血症促进了NLRP3炎性小体的激活，破坏了炎性细胞因子反应，并在牙周组织和体外加剧了氧化应激。别嘌呤醇治疗逆转了小鼠和巨噬细胞中的所有相关变化。
高尿酸血症可能通过尿酸诱导的牙周炎症和氧化应激加剧牙周炎。
