Article Impact Level: HIGH Data Quality: STRONG Summary of International Journal of Oral Science, 17(1), 25. https://doi.org/10.1038/s41368-025-00355-x Dr. Yafei Xiong et al.
Points
- This study found that cartilage oligomeric matrix protein (COMP) plays a central role in promoting abnormal collagen I accumulation in oral submucous fibrosis through its interaction with collagen XIV.
- Experiments showed that arecoline exposure upregulates COMP in human oral fibroblasts, boosting collagen I secretion and contributing to fibrosis progression in OSF patients.
- Knockdown of COMP significantly reduced collagen I production in vitro, while Comp-deficient mice showed decreased fibrosis following arecoline exposure, underscoring COMP’s functional importance.
- The study identifies COMP-positive fibroblasts as primary contributors to excessive collagen secretion, pointing to COMP as a potential therapeutic target for OSF.
- These findings suggest that disrupting the COMP–collagen XIV axis could help halt or reverse fibrosis in OSF and related fibrotic disorders, offering new treatment opportunities.
Summary
This study explores the molecular mechanisms behind oral submucous fibrosis (OSF), a disease marked by excessive collagen accumulation in the oral mucosa, leading to restricted mouth opening and increased cancer risk. Researchers identified the key role of cartilage oligomeric matrix protein (COMP) in mediating abnormal collagen deposition. Using RNA sequencing and immunofluorescence in OSF specimens, the study found that COMP interacts with collagen XIV, a member of the fibril-associated collagens with interrupted triple helices (FACIT) family, to drive collagen I accumulation. COMP was upregulated during the progression of OSF, particularly with arecoline stimulation. In vivo experiments with Comp-/- mice showed that the absence of COMP significantly reduced arecoline-induced collagen I deposition.
The study also highlighted that human oral buccal mucosal fibroblasts (hBMFs) exhibited increased COMP and collagen I secretion upon arecoline stimulation in vitro. Knockdown of COMP in these fibroblasts led to a marked decrease in collagen I secretion, suggesting that COMP plays a crucial role in collagen accumulation in OSF. Furthermore, the study demonstrated that COMP-positive fibroblasts secreted more collagen I, suggesting that targeting COMP could reverse or halt OSF progression. This interaction between COMP and collagen XIV, integral to the collagen network, presents a promising therapeutic target.
In summary, the study reveals that COMP mediates abnormal collagen I deposition through its interaction with collagen XIV, driving the progression of OSF. The findings suggest that targeting COMP could be a potential therapeutic strategy to address the excessive collagen buildup in OSF and other fibrotic conditions. The research holds promise for developing treatments that could prevent or reverse fibrosis in OSF, enhancing patient outcomes and quality of life.
Link to the article: https://www.nature.com/articles/s41368-025-00355-x
References Xiong, Y., Li, X., Sun, B., Zhang, J., Wu, X., & Guo, F. (2025). Abnormal collagen deposition mediated by cartilage oligomeric matrix protein in the pathogenesis of oral submucous fibrosis. International Journal of Oral Science, 17(1), 25. https://doi.org/10.1038/s41368-025-00355-x
