Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis.
10.1038/s41368-025-00355-x
- Author:
Yafei XIONG
1
;
Xuechun LI
2
;
Bincan SUN
2
;
Jie ZHANG
1
;
Xiaoshan WU
3
;
Feng GUO
4
,
5
Author Information
1. Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China.
2. Academician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South University, Changsha, China.
3. Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China. drwuxiaoshan@csu.edu.cn.
4. Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, China. dentguo@
5. com.
- Publication Type:Research Support, Non-U.S. Gov't
- MeSH:
Oral Submucous Fibrosis/pathology*;
Cartilage Oligomeric Matrix Protein/genetics*;
Animals;
Mice;
Humans;
Fibroblasts/metabolism*;
Collagen Type I/metabolism*;
Arecoline/pharmacology*;
Mouth Mucosa/metabolism*;
Cells, Cultured;
Fluorescent Antibody Technique
- From:
International Journal of Oral Science
2025;17(1):25-25
- CountryChina
- Language:English
-
Abstract:
Abnormal accumulation of collagen fibrils is a hallmark feature of oral submucous fibrosis (OSF). However, the precise characteristics and underlying mechanisms remain unclear, impeding the advancement of potential therapeutic approaches. Here, we observed that collagen I, the main component of the extracellular matrix, first accumulated in the lamina propria and subsequently in the submucosa of OSF specimens as the disease progressed. Using RNA-seq and Immunofluorescence in OSF specimens, we screened the cartilage oligomeric matrix protein (COMP) responsible for the abnormal collagen accumulation. Genetic COMP deficiency reduced arecoline-stimulated collagen I deposition significantly in vivo. In comparison, both COMP and collagen I were upregulated under arecoline stimulation in wild-type mice. Human oral buccal mucosal fibroblasts (hBMFs) also exhibited increased secretion of COMP and collagen I after stimulation in vitro. COMP knockdown in hBMFs downregulates arecoline-stimulated collagen I secretion. We further demonstrated that hBMFs present heterogeneous responses to arecoline stimulation, of which COMP-positive fibroblasts secrete more collagen I. Since COMP is a molecular bridge with Fibril-associated collagens with Interrupted Triple helices (FACIT) in the collagen network, we further screened and identified collagen XIV, a FACIT member, co-localizing with both COMP and collagen I. Collagen XIV expression increased under arecoline stimulation in wild-type mice, whereas it was hardly expressed in the Comp-/- mice, even with under stimulation. In summary, we found that COMP may mediates abnormal collagen I deposition by functions with collagen XIV during the progression of OSF, suggesting its potential to be targeted in treating OSF.
