Therapeutic potential of farnesoid X receptor agonists for modulating inflammation and periodontal regeneration.

IF 3.1 2区 医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE
Jie Huang, Huang Zhang, Xusheng Fan, Yongwu Wang
{"title":"Therapeutic potential of farnesoid X receptor agonists for modulating inflammation and periodontal regeneration.","authors":"Jie Huang, Huang Zhang, Xusheng Fan, Yongwu Wang","doi":"10.1007/s00784-024-06087-2","DOIUrl":null,"url":null,"abstract":"<p><strong>Objectives: </strong>Inflammation and osteoclast activity are important in various diseases, including periodontitis and osteoporosis. Farnesoid X receptor (FXR) has been identified as a promising target for modulating these processes. This study delved into the impact of FXR agonists on inflammation and periodontal regeneration using periodontitis models.</p><p><strong>Material and methods: </strong>The RAW264.7 and gingival fibroblast cells were divided into five groups: control, lipopolysaccharide (LPS), LPS combined with FXR agonist, LPS with si-FXR, and LPS with si-FXR alongside FXR agonist. FXR expression and pro-inflammatory cytokine levels were quantified. Osteoclast activity was evaluated by observing morphological alterations and tartrate-resistant acid phosphatase staining. The rats were used to establish periodontitis models and received varying doses of FXR agonist. Bone health metrics were assessed, and the expressions of runt-related transcription factor 2 (RUNX2), integrin-binding sialoprotein (IBSP), nuclear factor-kappa B (NF-kB), phosphorylated nuclear factor-kappa B (p-NF-kB), toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) were determined.</p><p><strong>Results: </strong>FXR suppressed the release of pro-inflammatory cytokines in both LPS-stimulated RAW264.7 and gingival fibroblast cells, while curbing osteoclastogenesis. In periodontitis rat models, FXR agonist administration caused notable enhancement in bone density. Moreover, FXR agonist mitigated periodontal inflammation, decreased periodontal index markers and suppressed the expressions of NF-kB, p-NF-kB, TLR4, and TLR2, but upregulated the expressions of RUNX2 and IBSP.</p><p><strong>Conclusion: </strong>The data underscores the potential of FXR agonists in attenuating inflammation and periodontal regeneration, both in vitro and in vivo. This suggests the potential therapeutic application of FXR agonists in conditions marked by inflammation and bone degradation.</p>","PeriodicalId":10461,"journal":{"name":"Clinical Oral Investigations","volume":"29 1","pages":"10"},"PeriodicalIF":3.1000,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical Oral Investigations","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00784-024-06087-2","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"DENTISTRY, ORAL SURGERY & MEDICINE","Score":null,"Total":0}
引用次数: 0

Abstract

Objectives: Inflammation and osteoclast activity are important in various diseases, including periodontitis and osteoporosis. Farnesoid X receptor (FXR) has been identified as a promising target for modulating these processes. This study delved into the impact of FXR agonists on inflammation and periodontal regeneration using periodontitis models.

Material and methods: The RAW264.7 and gingival fibroblast cells were divided into five groups: control, lipopolysaccharide (LPS), LPS combined with FXR agonist, LPS with si-FXR, and LPS with si-FXR alongside FXR agonist. FXR expression and pro-inflammatory cytokine levels were quantified. Osteoclast activity was evaluated by observing morphological alterations and tartrate-resistant acid phosphatase staining. The rats were used to establish periodontitis models and received varying doses of FXR agonist. Bone health metrics were assessed, and the expressions of runt-related transcription factor 2 (RUNX2), integrin-binding sialoprotein (IBSP), nuclear factor-kappa B (NF-kB), phosphorylated nuclear factor-kappa B (p-NF-kB), toll-like receptor 4 (TLR4), and toll-like receptor 2 (TLR2) were determined.

Results: FXR suppressed the release of pro-inflammatory cytokines in both LPS-stimulated RAW264.7 and gingival fibroblast cells, while curbing osteoclastogenesis. In periodontitis rat models, FXR agonist administration caused notable enhancement in bone density. Moreover, FXR agonist mitigated periodontal inflammation, decreased periodontal index markers and suppressed the expressions of NF-kB, p-NF-kB, TLR4, and TLR2, but upregulated the expressions of RUNX2 and IBSP.

Conclusion: The data underscores the potential of FXR agonists in attenuating inflammation and periodontal regeneration, both in vitro and in vivo. This suggests the potential therapeutic application of FXR agonists in conditions marked by inflammation and bone degradation.

求助全文
约1分钟内获得全文 求助全文
来源期刊
Clinical Oral Investigations
Clinical Oral Investigations 医学-牙科与口腔外科
CiteScore
6.30
自引率
5.90%
发文量
484
审稿时长
3 months
期刊介绍: The journal Clinical Oral Investigations is a multidisciplinary, international forum for publication of research from all fields of oral medicine. The journal publishes original scientific articles and invited reviews which provide up-to-date results of basic and clinical studies in oral and maxillofacial science and medicine. The aim is to clarify the relevance of new results to modern practice, for an international readership. Coverage includes maxillofacial and oral surgery, prosthetics and restorative dentistry, operative dentistry, endodontics, periodontology, orthodontics, dental materials science, clinical trials, epidemiology, pedodontics, oral implant, preventive dentistiry, oral pathology, oral basic sciences and more.
×
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:481959085
Book学术官方微信