Arrestin beta‐2 deficiency exacerbates periodontal inflammation by mediating activating transcription factor 6 activation and abnormal remodelling of the extracellular matrix

Abstract Aim To investigate the specific role of arrestin beta‐2 (ARRB2) in the progression of periodontitis and the underlying mechanisms. Materials and Methods Single‐cell RNA sequencing data were used to analyse gene expression in periodontal tissues from healthy controls and patients with periodontitis. Real‐time quantitative polymerase chain reaction, Western blotting and immunohistochemical staining were performed to detect the expression of ARRB2. Furthermore, a ligature‐induced periodontitis model was created. Using radiographic and histological methods, RNA sequencing and luciferase assay, the role of ARRB2 in periodontitis and the underlying mechanisms were explored. Finally, the therapeutic effect of melatonin, an inhibitor of activating transcription factor 6 (ATF6), on periodontitis in mice was assessed in both in vivo and in vitro experiments. Results ARRB2 expression was up‐regulated in inflammatory periodontal tissue. In the ligature‐induced mouse model, Arrb2 knockout exacerbated alveolar bone loss (ABL) and extracellular matrix (ECM) degradation. ARRB2 exerted a negative regulatory effect on ATF6 , an essential targeted gene. Melatonin ameliorated ABL and an imbalance in ECM remodelling in Arrb2 ‐deficient periodontitis mice. Conclusions ARRB2 mediates ECM remodelling via inhibition of the ATF6 signalling pathway, which ultimately exerts a protective effect on periodontal tissues.