Lipocalin-2 as a fundamental protein in type 2 diabetes and periodontitis in mice.

IF 4.2 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE Journal of periodontology Pub Date : 2024-08-27 DOI:10.1002/JPER.24-0215
Diana Laura Sólis-Suarez, Saúl Ernesto Cifuentes-Mendiola, Patricia González-Alva, Adriana Patricia Rodríguez-Hernández, Arnulfo Martínez-Dávalos, Fulgencio Eduardo Llamosas-Hernandez, Marycarmen Godínez-Victoria, Ana Lilia García-Hernández
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Abstract

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.

Plain language summary: 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.

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脂联素-2 是 2 型糖尿病和小鼠牙周炎的基本蛋白。
背景:脂联素-2(LCN-2)是一种骨生成素,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。本研究旨在通过评估牙槽骨损失、血糖控制、炎症和股骨脆性,研究 LCN-2 在与 2 型糖尿病(T2D)相关的牙周炎中的参与情况:方法:使用了一种伴有 T2D 和 LCN-2 浓度升高的小鼠牙周炎模型。使用抗 LCN-2 多克隆抗体抑制 LCN-2 的功能,并使用同种型免疫球蛋白 G 作为对照。通过显微 CT 对牙槽骨和股骨进行评估。测定葡萄糖代谢。采用酶联免疫吸附法对肺泡骨裂解液中的肿瘤坏死因子(TNF-α)和核因子卡巴-B配体受体激活剂(RANKL)水平进行量化,并采用流式细胞术对血清细胞因子进行量化。在股骨中进行了三点弯曲试验,并用酶联免疫吸附法测定了股骨裂解物中的 RANKL 水平:结果:在T2D-牙周炎小鼠体内对LCN-2进行功能性抑制,可减少颊面和腭面的牙槽骨损失,并保护剩余骨的微观结构,减少牙槽骨中的TNF-α和RANKL,降低高血糖、葡萄糖不耐受和胰岛素抵抗,并通过改善胰腺β细胞的功能增加胰岛素分泌。此外,这种抑制还能提高血清游离甘油水平,降低血清白细胞介素(IL)-6,增加血清IL-4,降低股骨脆性和股骨中RANKL的表达:结论:LCN-2参与了与T2D相关的牙周炎。在患有 T2D 和牙周炎的小鼠体内抑制其功能,可改善胰腺 β 细胞功能和葡萄糖代谢,降低炎性细胞因子和骨 RANKL 水平,从而保护股骨和牙槽骨的微结构。牙周炎是一种破坏性牙龈和牙槽骨疾病。在 T2D 和牙周炎中,LCN-2 的水平都会升高。我们利用小鼠 T2D 和牙周炎模型,研究了阻断 LCN-2 功能对这两种疾病各方面的影响。我们发现,这种抑制作用带来了显著的改善。首先,它通过减少局部炎症和骨吸收,减少了牙槽骨流失并保护了骨结构。其次,它改善了葡萄糖和脂质代谢,从而改善了血糖控制并降低了胰岛素抵抗。阻断 LCN-2 的功能还能减少全身炎症,增强骨的完整性。总之,我们的研究结果表明,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 的功能,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。以 LCN-2 为靶点可能是解决 T2D 和牙周炎有害影响的一种有前途的策略。
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来源期刊
Journal of periodontology
Journal of periodontology 医学-牙科与口腔外科
CiteScore
9.10
自引率
7.00%
发文量
290
审稿时长
3-8 weeks
期刊介绍: The Journal of Periodontology publishes articles relevant to the science and practice of periodontics and related areas.
期刊最新文献
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