Fibroblast derived C3 promotes the progression of experimental periodontitis through macrophage M1 polarization and osteoclast differentiation.
10.1038/s41368-025-00361-z
- Author:
Feilong REN
1
;
Shize ZHENG
1
;
Huanyu LUO
1
;
Xiaoyi YU
2
;
Xianjing LI
1
;
Shaoyi SONG
1
;
Wenhuan BU
3
;
Hongchen SUN
4
Author Information
1. Hospital of Stomatology, Jilin University, Changchun, China.
2. Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, China.
3. Jilin Provincial Key Laboratory of Tooth Development and Bone Remodeling, School and Hospital of Stomatology, Jilin University, Changchun, China. whbu@jlu.edu.cn.
4. Hospital of Stomatology, Jilin University, Changchun, China. hcsun@mail.jlu.edu.cn.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Animals;
Osteoclasts/cytology*;
Periodontitis/metabolism*;
Cell Differentiation;
Mice;
Fibroblasts/metabolism*;
Macrophages;
Disease Models, Animal;
Complement C3/metabolism*;
Humans;
Disease Progression;
Mice, Inbred C57BL;
Male;
Mice, Knockout
- From:
International Journal of Oral Science
2025;17(1):30-30
- CountryChina
- Language:English
-
Abstract:
Complement C3 plays a critical role in periodontitis. However, its source, role and underlying mechanisms remain unclear. In our study, by analyzing single-cell sequencing data from mouse model of periodontitis, we identified that C3 is primarily derived from periodontal fibroblasts. Subsequently, we demonstrated that C3a has a detrimental effect in ligature-induced periodontitis. C3ar-/- mice exhibited significantly less destruction of periodontal support tissues compared to wild-type mice, characterized by mild gingival tissue damage and reduced alveolar bone loss. This reduction was associated with decreased production of pro-inflammatory mediators and reduced osteoclast infiltration in the periodontal tissues. Mechanistic studies suggested that C3a could promote macrophage polarization and osteoclast differentiation. Finally, by analyzing single-cell sequencing data from the periodontal tissues of patients with periodontitis, we found that the results observed in mice were consistent with human data. Therefore, our findings clearly demonstrate the destructive role of fibroblast-derived C3 in ligature-induced periodontitis, driven by macrophage M1 polarization and osteoclast differentiation. These data strongly support the feasibility of C3a-targeted interventions for the treatment of human periodontitis.
