Unveiling the molecular landscape of dental caries and its impact on ECM remodeling

The rapid progression of caries lesions in dentin is facilitated by its reduced mineralization, high organic content, and tubular structure, contributing to ECM degradation through MMP activation in acidic conditions. This study investigates the expression of collagenases (MMP-2 and MMP-9) and their inhibitors (TIMP-1 and TIMP-2) in the pulp, predentin, and dentin of decayed teeth. RNA from these tissues was sequenced using Illumina® technology. Quality validation, read alignment to the human transcriptome, and differential gene expression analysis were performed. Gene Ontology and KEGG pathway analyses identified significant biological processes. Sequencing produced 16-37 million reads with 87.25%-88.08% alignment, identifying 1.01% of over 33,000 genes as differentially expressed. In decayed tissues, upregulated genes linked to detoxification and stress responses suggest adaptive mechanisms, while downregulated genes relate to energy metabolism and tooth development, indicating impaired enamel and dentin formation. Interaction network analysis underscores roles for proteins like EGFR and metallothioneins in acute-phase responses. Metabolic pathways involving ECM components underscore structural impacts of caries. MMP-2 is highly expressed in decayed predentin and dentin, while MMP-9 is reduced across all tissues. TIMP-1, predominantly in decayed dentin, aligns with its role as an MMP-9 inhibitor. TIMP-2, which inhibits MMP-2, shows elevated levels in both decayed and caries-free dentin, reflecting tissue-specific regulation. The expression of MMPs and TIMPs indicates a complex regulation of ECM degradation and repair. Upregulation of inflammatory and stress-related genes (SAA1, SAA2, ORM1, ORM2, SERPINA1), with the regulatory balance of MMPs and TIMPs, underscores their significant role in maintaining ECM integrity.