27- 羟基胆固醇在与高胆固醇血症相关的根尖牙周炎恶化中的作用以及非洛地平的治疗潜力。

IF 3.4 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Dental Sciences Pub Date : 2025-01-01 DOI:10.1016/j.jds.2024.09.027

Cheng-Ning Yang , Han-Wei Wang , Hung-Ying Lin , Sang-Heng Kok , Chi-Yuan Hong , Chia-Tung Shun , Shih-Jung Cheng , Fang-Yu Wu , Sze-Kwan Lin

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引用次数: 0

摘要

背景/目的：研究表明，高胆固醇血症与根尖牙周炎（AP）的发生有关，但其潜在机制尚不确定。众所周知，由细胞色素 P450 27A1 (CYP27A1) 催化胆固醇羟基化产生的 27- 羟基胆固醇（27HC）具有促炎活性。非洛地平是一种能够抑制 CYP27A1 的抗高血压药物。本研究旨在探讨巨噬细胞对 27HC 的炎症反应，以及 27HC 积累与实验性 AP 进展之间的关系。研究还评估了非洛地平的治疗效果：材料和方法：使用 J774 小鼠巨噬细胞。通过 Western 印迹检测环氧化酶-2（COX-2）和 C-C motif 趋化因子配体 20（CCL20）的表达。酶联免疫吸附试验评估了 27HC 的浓度。荧光检测法用于评估胆固醇水平。雄性大鼠接受高脂/高胆固醇饮食（HFHCD）或正常饮食（ND）诱导 AP。采用显微计算机断层扫描和免疫组织化学方法评估疾病进展和非洛地平的治疗效果：结果：胆固醇促进了 27HC 的产生，进而刺激了巨噬细胞合成 COX-2 和 CCL20。服用高频胆固醇胆固醇酯可明显提高大鼠血清和病变组织中 27HC 的水平。随着 27HC 在 AP 中的积累，病变大小以及 COX-2+ 和白细胞介素 (IL)-17+ 细胞的浸润也随之增加。非洛地平抑制了巨噬细胞中胆固醇诱导的 27HC 生成。非洛地平治疗可降低 HFHCD 大鼠血清和组织中的 27HC 水平，同时减轻 AP 的传播：我们的研究结果表明，27HC 在高胆固醇血症加重的 AP 中起着关键作用。通过抑制 27HC 的产生，非洛地平可能有助于减轻肥胖者的 AP。

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The role of 27-hydroxycholesterol in hypercholesterolemia-associated exacerbation of apical periodontitis and therapeutic potential of felodipine

Background/purpose

Studies have demonstrated a relation between hypercholesterolemia and development of apical periodontitis (AP), but the underlying mechanism is uncertain. 27-hydroxycholesterol (27HC), produced by cytochrome P450 27A1 (CYP27A1)-catalyzed hydroxylation of cholesterol, is known to possess pro-inflammatory activity. Felodipine is an anti-hypertensive agent able to inhibit CYP27A1. The study aimed to examine the inflammatory response of macrophages to 27HC and the relation between 27HC accumulation and progression of experimental AP. The therapeutic effect of felodipine was also evaluated.

Materials and methods

J774 murine macrophages were used. Expressions of cyclooxygenase-2 (COX-2) and C–C motif chemokine ligand 20 (CCL20) were examined by Western blot. Concentrations of 27HC were assessed by enzyme-linked immunosorbent assay. Fluorescence assay was used to evaluate cholesterol levels. AP was induced in male rats receiving high fat/high cholesterol diet (HFHCD) or normal diet (ND). Micro-computed tomography and immunohistochemistry were employed to evaluate disease progression and therapeutic effect of felodipine.

Results

Cholesterol enhanced production of 27HC which in turn stimulated COX-2 and CCL20 synthesis by macrophages. HFHCD consumption significantly augmented serum and lesion tissue levels of 27HC in rats. Lesion size and infiltration of COX-2⁺ and interleukin (IL)-17⁺ cells increased in parallel with 27HC accumulation in AP. Felodipine suppressed cholesterol-induced 27HC production in macrophages. Felodipine treatment reduced serum and tissue levels of 27HC in HFHCD rats and concurrently mitigated AP propagation.

Conclusion

Our results suggest a pivotal role of 27HC in hypercholesterolemia-exacerbated AP. By repressing 27HC production, felodipine may have the potential to help mitigate AP in obese individuals.

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来源期刊

Journal of Dental Sciences 医学-牙科与口腔外科

CiteScore

5.10

自引率

14.30%

发文量

348

审稿时长

6 days

期刊介绍： he Journal of Dental Sciences (JDS), published quarterly, is the official and open access publication of the Association for Dental Sciences of the Republic of China (ADS-ROC). The precedent journal of the JDS is the Chinese Dental Journal (CDJ) which had already been covered by MEDLINE in 1988. As the CDJ continued to prove its importance in the region, the ADS-ROC decided to move to the international community by publishing an English journal. Hence, the birth of the JDS in 2006. The JDS is indexed in the SCI Expanded since 2008. It is also indexed in Scopus, and EMCare, ScienceDirect, SIIC Data Bases. The topics covered by the JDS include all fields of basic and clinical dentistry. Some manuscripts focusing on the study of certain endemic diseases such as dental caries and periodontal diseases in particular regions of any country as well as oral pre-cancers, oral cancers, and oral submucous fibrosis related to betel nut chewing habit are also considered for publication. Besides, the JDS also publishes articles about the efficacy of a new treatment modality on oral verrucous hyperplasia or early oral squamous cell carcinoma.