Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis
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 componen...
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Nature Publishing Group
2025-03-01
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| Series: | International Journal of Oral Science |
| Online Access: | https://doi.org/10.1038/s41368-025-00355-x |
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| author | Yafei Xiong Xuechun Li Bincan Sun Jie Zhang Xiaoshan Wu Feng Guo |
| author_facet | Yafei Xiong Xuechun Li Bincan Sun Jie Zhang Xiaoshan Wu Feng Guo |
| author_sort | Yafei Xiong |
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| description | 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. |
| format | Article |
| id | doaj-art-1484feb9a10b43ea83569b2fbbaaef51 |
| institution | OA Journals |
| issn | 2049-3169 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | International Journal of Oral Science |
| spelling | doaj-art-1484feb9a10b43ea83569b2fbbaaef512025-08-20T02:10:16ZengNature Publishing GroupInternational Journal of Oral Science2049-31692025-03-0117111210.1038/s41368-025-00355-xAbnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosisYafei Xiong0Xuechun Li1Bincan Sun2Jie Zhang3Xiaoshan Wu4Feng Guo5Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South UniversityAcademician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South UniversityAcademician Workstation for Oral-Maxillofacial Regenerative Medicine, Central South UniversityDepartment of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South UniversityDepartment of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South UniversityDepartment of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South UniversityAbstract 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.https://doi.org/10.1038/s41368-025-00355-x |
| spellingShingle | Yafei Xiong Xuechun Li Bincan Sun Jie Zhang Xiaoshan Wu Feng Guo Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis International Journal of Oral Science |
| title | Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| title_full | Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| title_fullStr | Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| title_full_unstemmed | Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| title_short | Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| title_sort | abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis |
| url | https://doi.org/10.1038/s41368-025-00355-x |
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