Endocannabinoid system in periodontitis: A systematic review and in silico analyses

IF 2.1 4区 医学 Q2 DENTISTRY, ORAL SURGERY & MEDICINE
Lélio Fernando Ferreira Soares , Jovânia Alves Oliveira , Andressa Vilas Boas Nogueira , Carlos Rossa Júnior , Suzane Cristina Pigossi , James Deschner , Joni Augusto Cirelli
{"title":"Endocannabinoid system in periodontitis: A systematic review and in silico analyses","authors":"Lélio Fernando Ferreira Soares ,&nbsp;Jovânia Alves Oliveira ,&nbsp;Andressa Vilas Boas Nogueira ,&nbsp;Carlos Rossa Júnior ,&nbsp;Suzane Cristina Pigossi ,&nbsp;James Deschner ,&nbsp;Joni Augusto Cirelli","doi":"10.1016/j.archoralbio.2025.106394","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><div>This systematic review with in silico investigation discusses the involvement of the endocannabinoid system (ECS), particularly CB1 and CB2 receptors (genes <em>CNR1</em> and <em>CNR2</em> respectively), in periodontal health and disease (PD).</div></div><div><h3>Methods</h3><div>PubMed/MEDLINE, Embase, Web of Science, Scopus, and The Cochrane Library databases were searched for studies on periodontitis and ECS published up to August 2024. The GSE16134 dataset was used for analyses of differential gene expression, correlation of ECS genes, evaluation of biomarkers and functional enrichment analysis.</div></div><div><h3>Results</h3><div>Nine studies met the inclusion criteria (three clinical and six preclinical studies). Clinical studies demonstrated that <em>CNR2</em> gene expression was significantly reduced in periodontitis, while <em>CNR1</em> showed minor changes. Animal studies with CB2 activation by different therapies increased receptor expression, reduced pro-inflammatory cytokines, and mitigated alveolar bone loss. CB1 activation also reduced inflammation and bone loss. Anandamide (AEA), an endogenous ligand of the cannabinoid receptors, exhibited anti-inflammatory effects, with endogenous levels decreasing after therapy. Bioinformatics analysis revealed that <em>CNR1</em> expression in PD tissues was positively associated with genes involved in B-cell activation and humoral immune responses. In contrast, <em>CNR2</em> expression showed strong correlations with genes related to immune regulation and extracellular matrix remodeling, suggesting distinct yet complementary roles for CB1 and CB2 in periodontal inflammation.</div></div><div><h3>Conclusions</h3><div>The ECS participates in periodontal inflammation, with CB2 activation emerging as a promising therapeutic target.</div></div>","PeriodicalId":8288,"journal":{"name":"Archives of oral biology","volume":"179 ","pages":"Article 106394"},"PeriodicalIF":2.1000,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of oral biology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0003996925002225","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0

Abstract

Objective

This systematic review with in silico investigation discusses the involvement of the endocannabinoid system (ECS), particularly CB1 and CB2 receptors (genes CNR1 and CNR2 respectively), in periodontal health and disease (PD).

Methods

PubMed/MEDLINE, Embase, Web of Science, Scopus, and The Cochrane Library databases were searched for studies on periodontitis and ECS published up to August 2024. The GSE16134 dataset was used for analyses of differential gene expression, correlation of ECS genes, evaluation of biomarkers and functional enrichment analysis.

Results

Nine studies met the inclusion criteria (three clinical and six preclinical studies). Clinical studies demonstrated that CNR2 gene expression was significantly reduced in periodontitis, while CNR1 showed minor changes. Animal studies with CB2 activation by different therapies increased receptor expression, reduced pro-inflammatory cytokines, and mitigated alveolar bone loss. CB1 activation also reduced inflammation and bone loss. Anandamide (AEA), an endogenous ligand of the cannabinoid receptors, exhibited anti-inflammatory effects, with endogenous levels decreasing after therapy. Bioinformatics analysis revealed that CNR1 expression in PD tissues was positively associated with genes involved in B-cell activation and humoral immune responses. In contrast, CNR2 expression showed strong correlations with genes related to immune regulation and extracellular matrix remodeling, suggesting distinct yet complementary roles for CB1 and CB2 in periodontal inflammation.

Conclusions

The ECS participates in periodontal inflammation, with CB2 activation emerging as a promising therapeutic target.
内源性大麻素系统在牙周炎:系统回顾和计算机分析。
目的:本系统综述结合计算机研究探讨了内源性大麻素系统(ECS),特别是CB1和CB2受体(分别为CNR1和CNR2基因)在牙周健康和疾病(PD)中的作用。方法:检索PubMed/MEDLINE、Embase、Web of Science、Scopus和The Cochrane Library数据库,检索截至2024年8月发表的有关牙周炎和ECS的研究。GSE16134数据集用于差异基因表达分析、ECS基因相关性分析、生物标志物评估和功能富集分析。结果:9项研究符合纳入标准(3项临床研究和6项临床前研究)。临床研究表明,牙周炎患者CNR2基因表达显著降低,而CNR1基因表达变化较小。在动物实验中,通过不同的治疗方法激活CB2可以增加受体表达,减少促炎细胞因子,减轻牙槽骨丢失。CB1激活还能减少炎症和骨质流失。大麻素受体的内源性配体Anandamide (AEA)表现出抗炎作用,治疗后内源性水平降低。生物信息学分析显示,CNR1在PD组织中的表达与参与b细胞活化和体液免疫反应的基因呈正相关。相比之下,CNR2的表达与免疫调节和细胞外基质重塑相关的基因有很强的相关性,这表明CB1和CB2在牙周炎症中具有不同但互补的作用。结论:ECS参与牙周炎症,CB2激活成为一个有希望的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Archives of oral biology
Archives of oral biology 医学-牙科与口腔外科
CiteScore
5.10
自引率
3.30%
发文量
177
审稿时长
26 days
期刊介绍: Archives of Oral Biology is an international journal which aims to publish papers of the highest scientific quality in the oral and craniofacial sciences. The journal is particularly interested in research which advances knowledge in the mechanisms of craniofacial development and disease, including: Cell and molecular biology Molecular genetics Immunology Pathogenesis Cellular microbiology Embryology Syndromology Forensic dentistry
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信