The Roles of BMP-2 on Modulating Oral Mucosal Keratinization

Objectives: In clinical practice, adequate width of keratinized mucosa firmly bound to the underlying bone is demanded to maintain health and stability around teeth and implants. To investigate the overall differences between keratinized and non-keratinized mucosa, which may be associated with mechanisms mediating the keratinization of mucosal epithelium, we performed bulk RNA-seq analysis and aimed to provide new insights into the regulatory networks of the keratinization process.
Methods: Collected keratinized (n=10*3) and non-keratinized (n=10*3) tissues from murine oral mucosa were compared by Bulk RNA-seq, and the differentially expressed genes (DEGs) were identified and enriched into several signaling pathways. We subsequently confirmed the role of a potential regulator BMP-2 (Bone Morphogenetic Protein 2) in promoting keratinization using TR146 cells grown at the Air-Liquid Interface (ALI) cell culture model.
Results: The analysis revealed 1624 DEGs in the epithelium and 2255 DEGs in the lamina propria when comparing keratinized to non-keratinized mucosa. Based on the DEGs and Gene Ontology enrichment analysis, an important osteoblast differentiation stimulator BMP-2 was identified to be potentially involved in oral mucosal keratinization. In ALI cell culture, the gene expression of keratinized markers KRT10 and IVL was significantly increased by treatment of BMP-2 in epithelial cells (Student t-test, p<0.05). Furthermore, we found several potential target genes downstream of BMP-2 that have been reported to be multifunctional in modulating the keratinization and proliferation process.
Conclusions: This study elucidates the overall variations between Keratinized and Non-keratinized mucosa. Moreover, we identify BMP-2 as a pivotal differentiation activator of oral keratinocytes via its potential downstream target genes, which shed light on the further usage of BMP-2 in clinical works.