Lipocalin-2 (LCN-2) 是一种骨因子，可抑制食欲、刺激胰岛素分泌、调节骨重塑，并由促炎细胞因子诱导。这项工作的目的是通过评估牙槽骨丢失、血糖控制、炎症和股骨脆性来研究 LCN-2 在与 2 型糖尿病 (T2D) 相关的牙周炎中的参与。 T2D 和 LCN- 升高的小鼠牙周炎模型使用2浓度。使用抗LCN-2多克隆抗体实现功能性LCN-2抑制，并使用同种型免疫球蛋白G作为对照。通过显微 CT 评估牙槽骨和股骨。测定葡萄糖代谢。使用 ELISA 定量牙槽骨裂解物中的肿瘤坏死因子 (TNF-α) 和核因子 kappa-B 配体受体激活剂 (RANKL) 水平，并使用流式细胞术定量血清细胞因子。在股骨中进行三点弯曲测试，并使用 ELISA 测量股骨裂解物中的 RANKL 水平。T2D 牙周炎小鼠中 LCN-2 的功能抑制减少了颊面和腭面的牙槽骨损失，并保留了剩余部分的微结构骨，减少牙槽骨中的 TNF-α 和 RANKL，减少高血糖、葡萄糖耐受不良和胰岛素抵抗，并通过改善胰腺 β 细胞的功能来增加胰岛素的产生。此外，这种抑制增加了血清游离甘油水平，降低了血清白细胞介素（IL）-6，增加了血清IL-4，并降低了股骨脆性和股骨中的RANKL表达。LCN-2参与与T2D相关的牙周炎。在患有 T2D 和牙周炎的小鼠中抑制其功能可改善胰腺 β 细胞功能和葡萄糖代谢，并降低炎症细胞因子和骨 RANKL 水平，从而保护股骨和牙槽骨微结构。在本研究中，我们探讨了一种称为脂质运载蛋白-2 (LCN-2) 的骨蛋白与牙周炎和 2 型糖尿病 (T2D) 之间的关系有关。牙周炎是一种破坏性牙龈和牙槽骨疾病。 T2D 和牙周炎中 LCN-2 水平均升高。使用患有牙周炎的 T2D 小鼠模型，我们研究了阻断 LCN-2 功能如何影响这两种疾病的各个方面。我们发现这种抑制带来了显着的改善。首先，它通过减少局部炎症和骨吸收来减少牙槽骨丢失并保留骨结构。其次，它改善了葡萄糖和脂质代谢，从而更好地控制血糖并降低胰岛素抵抗。阻断 LCN-2 的功能还可以减少全身炎症并增强骨骼完整性。总体而言，我们的结果表明 LCN-2 在与 T2D 相关的牙周炎中发挥着至关重要的作用。通过抑制 LCN-2 功能，我们能够改善胰腺功能、改善葡萄糖代谢、减少炎症并增强骨骼健康。针对 T2D 和牙周炎的有害影响，针对 LCN-2 可能是一种有前景的策略。© 2024 作者。 《牙周病学杂志》由 Wiley periodicals LLC 代表美国牙周病学会出版。

Lipocalin-2 (LCN-2) is an osteokine that suppresses appetite, stimulates insulin secretion, regulates bone remodeling, and is induced by proinflammatory cytokines. The aim of this work was to investigate the participation of LCN-2 in periodontitis associated with type 2 diabetes (T2D) by evaluating alveolar bone loss, glycemic control, inflammation, and femur fragility.A murine model of periodontitis with T2D and elevated LCN-2 concentration was used. Functional LCN-2 inhibition was achieved using an anti-LCN-2 polyclonal antibody, and isotype immunoglobulin G was used as a control. The alveolar bone and femur were evaluated by micro-CT. Glucose metabolism was determined. Tumor necrosis factor (TNF-α) and receptor activator of nuclear factor kappa-B ligand (RANKL) levels in alveolar bone lysates were quantified using ELISA, and serum cytokines were quantified using flow cytometry. A three-point bending test was performed in the femur, and RANKL levels were measured in femur lysates using ELISA.Functional inhibition of LCN-2 in T2D-periodontitis mice decreased alveolar bone loss in buccal and palatal surfaces and preserved the microarchitecture of the remaining bone, decreased TNF-α and RANKL in alveolar bone, reduced hyperglycemia, glucose intolerance, and insulin resistance, and increased insulin production through improving the functionality of pancreatic β cells. Furthermore, this inhibition increased serum free-glycerol levels, decreased serum interleukin (IL)-6, increased serum IL-4, and reduced femur fragility and RANKL expression in the femur.LCN-2 participates in periodontitis associated with T2D. Inhibiting its function in mice with T2D and periodontitis improves pancreatic β-cell function, and glucose metabolism and decreases inflammatory cytokines and bone-RANKL levels, which results in the preservation of femoral and alveolar bone microarchitecture.In this study, we explored the role of a bone protein known as lipocalin-2 (LCN-2) in the connection between periodontitis and type 2 diabetes (T2D). Periodontitis is a destructive gum and alveolar bone disease. LCN-2 levels are increased in both T2D and periodontitis. Using a mouse model of T2D with periodontitis, we examined how blocking LCN-2 function affected various aspects of these two diseases. We found that this inhibition led to significant improvements. First, it reduced alveolar bone loss and preserved bone structure by decreasing local inflammation and bone resorption. Second, it improved glucose and lipid metabolism, leading to better blood-sugar control and decreased insulin resistance. Blocking the functions of LCN-2 also decreased systemic inflammation throughout the body and strengthened bone integrity. Overall, our results suggest that LCN-2 plays a crucial role in the periodontitis associated with T2D. By inhibiting LCN-2 function, we were able to improve pancreatic function, improve glucose metabolism, reduce inflammation, and enhance bone health. Targeting LCN-2 could be a promising strategy for the harmful effects of T2D and periodontitis.© 2024 The Author(s). Journal of Periodontology published by Wiley Periodicals LLC on behalf of American Academy of Periodontology.