Chongqing Key Laboratory for Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory for Oral Biomedical Engineering of Higher Education, and Stomatological Hospital of Chongqing Medical University, Chongqing, China.
Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
J Clin Periodontol. 2022 Oct;49(10):1052-1066. doi: 10.1111/jcpe.13667. Epub 2022 Jul 19.
To explore the role of C-reactive protein (CRP) in periodontitis and diabetes and its mechanism in alveolar bone homeostasis.
In vivo, normal, and Crp knockout (KO) rats were randomly divided into control, diabetes, periodontitis, and diabetes and periodontitis groups, respectively. The diabetes model was established using a high-fat diet combined with streptozotocin injection. The periodontitis model was established by ligature combined with lipopolysaccharide (LPS) injection. Alveolar bones were analysed using micro-computed tomography, histology, and immunohistochemistry. In vitro, human periodontal ligament cells (hPDLCs) were treated with LPS and high glucose. CRP knockdown lentivirus or CRP overexpression adenovirus combined with a PI3K/AKT signalling inhibitor or agonist were used to explore the regulatory mechanism of CRP in osteogenesis and osteoclastogenesis of hPDLCs, as evidenced by alkaline phosphatase staining, Western blot, and quantitative polymerase chain reaction.
In periodontitis and diabetes, CRP KO decreased the alveolar bone loss and the expression levels of osteoclastogenic markers, while increasing the expression levels of osteogenic markers. CRP constrained osteogenesis while promoting the osteoclastogenesis of hPDLCs via PI3K/AKT signalling under high glucose and pro-inflammatory conditions.
CRP inhibits osteogenesis and promotes osteoclastogenesis via PI3K/AKT signalling under diabetic and pro-inflammatory conditions, thus perturbing alveolar bone homeostasis.
探讨 C 反应蛋白（CRP）在牙周炎和糖尿病中的作用及其在牙槽骨稳态中的机制。
体内实验中，将正常和 Crp 基因敲除（KO）大鼠随机分为对照组、糖尿病组、牙周炎组和糖尿病合并牙周炎组。采用高脂饮食联合链脲佐菌素注射建立糖尿病模型，结扎联合脂多糖（LPS）注射建立牙周炎模型。采用微计算机断层扫描、组织学和免疫组织化学分析牙槽骨。体外实验中，用 LPS 和高葡萄糖处理人牙周膜细胞（hPDLCs）。用 CRP 敲低慢病毒或 CRP 过表达腺病毒联合 PI3K/AKT 信号通路抑制剂或激动剂，通过碱性磷酸酶染色、Western blot 和定量聚合酶链反应来探讨 CRP 对 hPDLCs 成骨和破骨分化的调节机制。
在牙周炎合并糖尿病中，CRP KO 减少了牙槽骨丢失和破骨细胞标志物的表达水平，同时增加了成骨标志物的表达水平。CRP 在高糖和促炎条件下通过 PI3K/AKT 信号通路抑制成骨，同时促进 hPDLCs 的破骨分化。
CRP 在糖尿病和促炎条件下通过 PI3K/AKT 信号通路抑制成骨，促进破骨分化，从而破坏牙槽骨稳态。
