Type 2 Diabetes Mellitus Aggravates Pathological Damage in Chronic Pulpitis: Association with AGEs/RAGE-MAPK Signaling Pathway Activation

Objective This study aims to examine the influence of type 2 diabetes mellitus (T2DM) on the pathological progression of chronic pulpitis and to explores the associated molecular mechanisms. Methods In this study, transcriptome sequencing was performed on human clinical dental pulp samples. To validate the transcriptomic findings and investigate the underlying mechanisms, seventy-two Sprague Dawley rats were randomly allocated into four groups: normal control (Control), chronic pulpitis (PULP), T2DM, and T2DM combined with chronic pulpitis (T2DM+PULP). T2DM was induced by a high-fat diet combined with streptozotocin (STZ) injection, while chronic pulpitis was induced by local lipopolysaccharide (LPS) stimulation of the dental pulp. Histological, ultrastructural, immunological, and apoptosis analyses were conducted on rat tissues to assess the impact of T2DM on chronic pulpitis.act of T2DM on chronic pulpitis at various levels. Results Transcriptomic analysis of human samples showed that differentially expressed genes were enriched in the MAPK pathway. Due to limited human samples, validation was done in rats, where AGEs/RAGE expression and ERK/p38 phosphorylation increased, but total ERK/p38 did not change. H&E staining indicated more inflammation, necrosis, and vascular dilation in the T2DM+PULP group compared to PULP alone. TNF-α, IL-1β, and S100A8 levels rose significantly. TEM showed mitochondrial damage and basement membrane thickening with increased VEGF. Masson staining revealed reduced collagen, higher MMP-9, and lower TGF-β1. TUNEL and Western blot confirmed increased apoptosis, with elevated Bax/cleaved caspase-3 and reduced Bcl-2. Conclusion T2DM is associated with exacerbated pathological damage in chronic pulpitis, coinciding with elevated AGEs/RAGE expression and MAPK pathway activation.