Abstract
Periodontitis is a chronic inflammatory disease characterized by collagen degradation and alveolar bone loss. Although estrogen contributes to periodontal homeostasis, the role of the membrane-bound G protein-coupled estrogen receptor 30 (GPR30) in periodontitis remains unclear. This study investigated the temporal involvement of GPR30 in ligature-induced periodontitis, focusing on alveolar bone changes, collagen integrity, fibroblast activation, and epigenetic regulation. Twenty male Wistar rats were allocated to control and periodontitis groups and evaluated at days 7, 14, and 21 following placements of a stainless-steel ligature around the maxillary first molars. Alveolar bone loss was assessed radiographically, while inflammatory changes and collagen organization were examined using hematoxylin-eosin and Masson's trichrome staining. Immunohistochemistry was performed to evaluate GPR30, collagen I/III, α-smooth muscle actin (α-SMA), and histone modifications. Statistical analysis was conducted using one-way ANOVA with Tukey's post hoc test. Alveolar bone loss and collagen degradation were detectable on day 7 and peaked at day 14. GPR30 expression increased during the active inflammatory phase, accompanied by elevated α-SMA and histone H4 lysine 8 crotonylation (H4K8cr), and declined by day 21. Fibroblast transiently adopted a myofibroblast phenotype during inflammation and regressed during early tissue repair. Temporal changes in H4K8cr closely paralleled GPR30 expression. These findings indicate that GPR30 is dynamically associated with inflammatory and remodeling phases of periodontitis and may contribute to epigenetic regulation during periodontal tissue remodeling.