Sólis-Suarez Diana Laura, Cifuentes-Mendiola Saúl Ernesto, González-Alva Patricia, Rodríguez-Hernández Adriana Patricia, Martínez-Dávalos Arnulfo, Llamosas-Hernandez Fulgencio Eduardo, Godínez-Victoria Marycarmen, García-Hernández Ana Lilia
Laboratory of Dental Research, Section of Osteoimmunology and Oral Immunology, FES Iztacala, National Autonomous University of Mexico (UNAM), State of Mexico, Mexico, Mexico.
Postgraduate Course in Dental Sciences, National Autonomous University of Mexico, Mexico City, Mexico.
J Periodontol. 2025 Apr;96(4):369-382. doi: 10.1002/JPER.24-0215. Epub 2024 Aug 27.
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.
脂联素 -2（LCN -2）是一种骨调节素，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产生。本研究旨在通过评估牙槽骨丧失、血糖控制、炎症和股骨脆性，来探究LCN -2在2型糖尿病（T2D）相关牙周炎中的作用。
使用患有T2D且LCN -2浓度升高的牙周炎小鼠模型。使用抗LCN -2多克隆抗体实现LCN -2的功能性抑制，并使用同型免疫球蛋白G作为对照。通过显微CT评估牙槽骨和股骨。测定葡萄糖代谢情况。使用酶联免疫吸附测定（ELISA）法定量牙槽骨裂解物中的肿瘤坏死因子（TNF -α）和核因子κB受体活化因子配体（RANKL）水平，并使用流式细胞术对血清细胞因子进行定量。对股骨进行三点弯曲试验，并使用ELISA法测量股骨裂解物中的RANKL水平。
对T2D -牙周炎小鼠的LCN -2进行功能性抑制，可减少颊侧和腭侧牙槽骨丧失，并保留剩余骨的微结构，降低牙槽骨中的TNF -α和RANKL水平，减轻高血糖、葡萄糖不耐受和胰岛素抵抗，并通过改善胰腺β细胞功能增加胰岛素分泌。此外，这种抑制作用可提高血清游离甘油水平，降低血清白细胞介素（IL）-6水平，提高血清IL -4水平，并降低股骨脆性以及股骨中RANKL的表达。
LCN -2参与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，降低炎性细胞因子和骨RANKL水平，从而保留股骨和牙槽骨的微结构。
在本研究中，我们探究了一种名为脂联素 -2（LCN -2）的骨蛋白在牙周炎与2型糖尿病（T2D）之间的联系中所起的作用。牙周炎是一种破坏性的牙龈和牙槽骨疾病。在T2D和牙周炎中，LCN -2水平都会升高。我们使用患有牙周炎的T2D小鼠模型，研究了阻断LCN -2功能如何影响这两种疾病的各个方面。我们发现这种抑制作用带来了显著改善。首先，它通过减少局部炎症和骨吸收，降低了牙槽骨丧失并保留了骨结构。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的功能还可减轻全身的系统性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相关的牙周炎中起关键作用。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、减轻炎症并增强骨骼健康。针对LCN -2可能是应对T2D和牙周炎有害影响的一种有前景的策略。
