Journal of Inflammation Research (Jul 2023)
Interactions of Fibroblast Subtypes Influence Osteoclastogenesis and Alveolar Bone Destruction in Periodontitis
Abstract
Haicheng Wang,1,* Renbin Wang,2,* Jingwen Yang,3– 5 Yuan Feng,6 Shuyu Xu,6 Qing-Guo Pei7 1Department of Pathology, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 2Department of Gastroenterology, The People’s Hospital of Zhongjiang, Zhongjiang, Sichuan Province, 618100, People’s Republic of China; 3Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, 100081, People’s Republic of China; 4National Center of Stomatology & National Clinical Research Center for Oral Diseases, Beijing, 100081, People’s Republic of China; 5National Engineering Research Center of Oral Biomaterials and Digital Medical Devices, Beijing, 100081, People’s Republic of China; 6Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai, 200072, People’s Republic of China; 7Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shuyu Xu, Department of Oral Implantology, School of & Hospital Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, 399 Yanchang Road, Shanghai, 200072, People’s Republic of China, Tel +86-21-66313725/(8610) ; +8618616308949, Email [email protected] Qing-Guo Pei, Department of Stomatology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Hongkou District, Shanghai, 200080, People’s Republic of China, Tel +86-21-37798330/(8610) ; +8613764521025, Email [email protected]: To analyze the fibroblasts subtypes in the gingival tissues of healthy controls, gingivitis and periodontitis patients, as well as the effects of interaction between subtypes on alveolar bone destruction.Methods: Gingival tissues were divided into three groups according to clinical and radiographic examination, and the immunostaining of EDA+FN was assessed. Fibroblasts from gingiva developed colony formation units (CFUs) and induced Trap+MNCs. The expression of osteoclastogenesis-related genes was assessed by real-time PCR. Variances in the gene profiles of CFUs were identified by principal component analysis, and cluster analysis divided CFUs into subtypes. The induction of Trap+MNCs and gene expression were compared among individual or cocultured subtypes. The fibroblast subtypes exerted critical effect on Trap+MNCs formation were selected and edited by CRISPR/Cas to investigate the influence on osteoclastogenesis in the periodontitis in mice.Results: Most periodontitis samples exhibited intensive EDA+FN staining (P < 0.05), and these fibroblasts also induced most Trap+MNCs among three groups; consistently, fibroblasts from periodontitis highly expressed genes facilitating osteoclastogenesis. According to gene profiles and osteoclastogenic induction, four clusters of CFUs were identified. The proportion of clusters was significantly different (P < 0.05) among three groups, and their interaction influenced osteoclastogenic induction. Although Cluster 4 induced less osteoclasts, it enhanced the effects of Clusters 1 and 3 on Trap+MNCs formation (P < 0.05). EDA knockout in Cluster 4 abrogated this promotion (P < 0.05), and decreased osteoclasts and alveolar bone destruction in experimental periodontitis (P < 0.05).Conclusion: Heterogeneous fibroblast subtypes affect the switch or development of periodontitis. A subtype (Cluster 4) played important role during alveolar bone destruction, by regulating other subtypes via EDA+FN paracrine.Keywords: periodontitis, heterogeneity, fibroblast subtype, osteoclastogenesis, alveolar bone destruction
