Related Experiment Video
Updated: Jul 8, 2026
Inducing Apical Periodontitis in Mice
Published on: August 6, 2019
Pinocembrin Alleviates Gingival Fibroblast Senescence in a Mouse Model of Periodontitis Via CYP1B1 Downregulation
Zehao Chen1, Qianwen Tang1, Ruoshu Tang1
1Department of Stomatology, Nanfang Hospital, Southern Medical University, Guangzhou, China; Department of Periodontics, Stomatological Hospital, School of Stomatology, Southern Medical University, Guangzhou, PR China.
Introduction And Aims:
The severity of periodontitis, a chronic inflammatory disease, correlates with gingival tissue senescence. This study aimed to characterise the heterogeneous functions of these senescent cells and to define the mechanisms driving gingival fibroblast (GF) senescence, thereby assessing cellular senescence as a potential therapeutic target.
Methods:
We analysed cellular senescence changes in gingival tissues during periodontitis by integrating human gingival single-cell RNA sequencing (scRNA-seq) datasets. Biomarkers for a senescence-based diagnostic model for periodontitis were identified, and a potential drug targeting a key biomarker was screened. The effects of this drug on GF senescence were validated using an in vitro model induced by lipopolysaccharide (LPS) in primary human GFs (hGFs), alongside an in vivo experimental periodontitis mouse model induced by ligature.
Results:
ScRNA-seq revealed an increase in senescence across various cell types in periodontitis-affected gingival tissues, with GFs being the predominant senescent cell population. Senescence levels in GFs were elevated in both human and mouse periodontitis tissues. A diagnostic model for periodontitis was developed based on a cellular senescence-associated 3-gene signature. Further mechanistic investigation showed that CYP1B1 drives LPS-induced hGF senescence by suppressing fatty acid metabolism. Ultimately, pinocembrin was found to attenuate senescence of GFs and ameliorate experimental periodontitis in mice, an effect mediated primarily through the downregulation of CYP1B1.
Conclusion:
Cellular senescence is increased in gingival tissues during periodontitis. Targeting senescent GFs presents a promising therapeutic strategy for the treatment of periodontitis.
Clinical Relevance:
Periodontitis-related tissue destruction involves cellular senescence, yet the responsible gingival cell populations and molecular mechanisms remain undefined. CYP1B1-driven suppression of fatty acid metabolism underlies gingival fibroblast senescence, the predominant senescent process in periodontitis, and is attenuated by pinocembrin. CYP1B1 represents a novel therapeutic target for periodontitis. Pinocembrin warrants further preclinical evaluation as a promising adjunct to periodontal therapy.
