Abstract
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.
Keywords:
Gelatinases; Isobutyric acid; Microbial metabolite; NF-κB signalling; Periodontitis.