背景:Lipocalin-2(LCN-2)是一种抑制食欲的趋化因子,刺激胰岛素分泌,调节骨骼重塑,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来研究LCN-2在与2型糖尿病(T2D)相关的牙周炎中的参与,血糖控制,炎症,股骨脆弱。
方法:使用具有T2D和升高的LCN-2浓度的牙周炎小鼠模型。使用抗LCN-2多克隆抗体实现功能性LCN-2抑制,和同种型免疫球蛋白G用作对照。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κB配体受体活化因子(RANKL)水平。使用流式细胞术对血清细胞因子进行定量。在股骨中进行三点弯曲测试,使用ELISA测量股骨裂解物中的RANKL水平。
结果:T2D-牙周炎小鼠中LCN-2的功能性抑制减少了口腔和腭表面的牙槽骨损失,并保留了剩余骨的微结构,牙槽骨中TNF-α和RANKL降低,减少高血糖,葡萄糖不耐受,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,这种抑制作用增加了血清游离甘油水平,血清白细胞介素(IL)-6降低,血清IL-4升高,股骨脆性和股骨RANKL表达降低。
结论:LCN-2参与了与T2D相关的牙周炎。在T2D和牙周炎小鼠中抑制其功能可改善胰腺β细胞功能,和葡萄糖代谢,并降低炎性细胞因子和骨RANKL水平,这导致股骨和牙槽骨微结构的保存。
结论:在这项研究中,我们探讨了一种称为脂质运载蛋白2(LCN-2)的骨蛋白在牙周炎和2型糖尿病(T2D)之间的关系中的作用.牙周炎是一种破坏性的牙龈和牙槽骨疾病。LCN-2水平在T2D和牙周炎中均升高。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。我们发现这种抑制导致显著的改善。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。第二,它改善了葡萄糖和脂质代谢,导致更好的血糖控制和降低胰岛素抵抗。阻断LCN-2的功能还减少了全身的全身性炎症并加强了骨完整性。总的来说,我们的结果表明LCN-2在与T2D相关的牙周炎中起着至关重要的作用.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,增强骨骼健康。靶向LCN-2可能是T2D和牙周炎有害影响的有希望的策略。
BACKGROUND: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
CONCLUSIONS: 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.