Epiregulin enhances periodontal tissue regeneration by promoting bone marrow mesenchymal stem cell functions under inflammatory niches

BACKGROUND: Mesenchymal stem cells are promising regenerative therapies; however, inflammation often impairs their function. Epiregulin (EREG), a member of the epidermal growth factor family, regulates cell migration, differentiation, and tissue repair. However, its effects on periodontal tissue regeneration using mouse bone marrow stem cells (mBMSCs) under inflammatory conditions remain unclear. We hypothesized that EREG activates epidermal growth factor receptor (EGFR)-extracellular signal-regulated kinase 1/2 (ERK1/2) in inflammatory conditions to improve mBMSC function and periodontitis treatment results. AIM: To investigate EREG's role in periodontal tissue regeneration, aiming to identify therapeutic targets for periodontal treatment. METHODS: Tumor necrosis factor alpha stimulates inflammation. Lentiviral short hairpin RNA inhibited EGFR expression. Scratch wounds, Transwell assays, Alizarin Red staining, and Western blotting were used to assess the effects and mechanisms of EREG on the migration, chemotaxis, and osteogenic differentiation capacity of mBMSCs. Micro-computed tomography and histological staining evaluated periodontal tissue regeneration. RESULTS: EREG enhances the migration, chemotaxis, and osteogenic differentiation of mBMSCs under inflammatory conditions. Mechanistically, EREG binds to EGFR and activates the ERK1/2 signaling pathway to stimulate these functions. Local administration of EREG facilitated periodontal tissue regeneration in a rat model of periodontitis. CONCLUSION: the EREG-EGFR-ERK1/2 pathway under inflammatory conditions and facilitates periodontal tissue regeneration.