异丁酸通过NF-κB信号传导调节人牙周韧带干细胞明胶酶分泌

IF 3.7 3区医学 Q1 DENTISTRY, ORAL SURGERY & MEDICINE

International dental journal Pub Date : 2025-10-21 DOI:10.1016/j.identj.2025.103966

Ying Tu , Xiaoyao Fu , Xinjie Ning , Huiling Zheng , Li Zhang , Qiang Guo , Minglei Huang , Hanxi Cao , Haoran Chen , Yonglu Jia , Mengmeng Duan , Yang Liu , Caixia Pi , Biao Ren , Chengcheng Liu , Jing Xie

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Isobutyric acid local injection models in 5-week-old male Sprague‒Dawley rats and an isobutyric acid treatment model of human periodontal ligament stem cells (hPDLSCs) were established to explore the effect of isobutyric acid on periodontal tissue destruction. Alveolar bone resorption in the rats was evaluated via microcomputed tomography. The activity and expression of gelatinases (MMP-2/MMP-9) and signalling proteins in hPDLSCs and periodontal tissues were detected via zymography, western blotting, immunofluorescence, and immunohistochemistry.</div></div><div><h3>Results</h3><div>A higher concentration of isobutyric acid was detected in the saliva of individuals with gingivitis and periodontitis than in that of healthy individuals. Local injection of isobutyric acid induced damage to periodontal soft tissues and increased resorption of alveolar bone in rats. 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引用次数: 0

摘要

背景：牙周炎主要是由细菌生态失调引起的炎症。异丁酸是一种主要来源于牙龈下病原菌的代谢物，可诱导细胞凋亡和癌细胞转移。然而，它在牙周炎中的作用仍然难以捉摸。本研究的目的是探讨异丁酸对牙周组织破坏的影响及其潜在的机制。方法：采用液相色谱-质谱联用法测定临床受试者唾液中异丁酸的浓度。建立异丁酸局部注射5周龄雄性sd大鼠模型和异丁酸治疗人牙周韧带干细胞（hPDLSCs）模型，探讨异丁酸对牙周组织破坏的影响。通过微计算机断层扫描评估大鼠牙槽骨吸收。通过酶谱法、western blotting、免疫荧光和免疫组织化学检测hPDLSCs和牙周组织中明胶酶（MMP-2/MMP-9）和信号蛋白的活性和表达。结果：牙龈炎和牙周炎患者唾液中异丁酸浓度高于健康人。局部注射异丁酸可引起大鼠牙周软组织损伤和牙槽骨吸收增加。在体外条件下，异丁酸增加了hPDLSCs中明胶酶的活性，异丁酸调节明胶酶的分泌主要通过激活NF-κB （p-p65）信号传导。研究了异丁酸对大鼠牙周组织明胶酶和NF-κB （p-p65）表达的影响。结论：本研究揭示了代谢物异丁酸通过调节明胶酶活性与hPDLSCs直接相互作用，部分解释了牙周组织降解和牙槽骨吸收的原因。

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Isobutyric Acid Regulates Gelatinase Secretion by Human Periodontal Ligament Stem Cells Via NF-κB Signalling

Background

Periodontitis is primarily an inflammatory condition initiated by bacterial dysbiosis. Isobutyric acid, a metabolite derived mainly from subgingival pathogenic bacteria, induces apoptosis and cancer cell metastasis. However, its role in periodontitis remains elusive. The aim of this study was to investigate the effects of isobutyric acid on the destruction of periodontal tissue and the underlying mechanisms involved.

Methods

The concentration of isobutyric acid in the saliva of clinical subjects was detected via liquid chromatography‒mass spectrometry. Isobutyric acid local injection models in 5-week-old male Sprague‒Dawley rats and an isobutyric acid treatment model of human periodontal ligament stem cells (hPDLSCs) were established to explore the effect of isobutyric acid on periodontal tissue destruction. Alveolar bone resorption in the rats was evaluated via microcomputed tomography. The activity and expression of gelatinases (MMP-2/MMP-9) and signalling proteins in hPDLSCs and periodontal tissues were detected via zymography, western blotting, immunofluorescence, and immunohistochemistry.

Results

A higher concentration of isobutyric acid was detected in the saliva of individuals with gingivitis and periodontitis than in that of healthy individuals. Local injection of isobutyric acid induced damage to periodontal soft tissues and increased resorption of alveolar bone in rats. Under in vitro conditions, isobutyric acid increased the activity of gelatinases in hPDLSCs, and isobutyric acid-regulated gelatinase secretion occurred mainly via the activation of NF-κB (p-p65) signalling. In rat periodontal tissues, the effects of isobutyric acid on the expression of gelatinases and NF-κB (p-p65) were verified.

Conclusion

This study revealed a direct interaction between the metabolite isobutyric acid and hPDLSCs through the regulation of the activity of gelatinases, which partially explains the degradation of periodontal tissue and resorption of alveolar bone.

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来源期刊

International dental journal 医学-牙科与口腔外科

CiteScore

4.80

自引率

6.10%

发文量

159

审稿时长

63 days

期刊介绍： The International Dental Journal features peer-reviewed, scientific articles relevant to international oral health issues, as well as practical, informative articles aimed at clinicians.