Hyperglycaemia aggravates periodontal inflamm‐aging by promoting SETDB1‐mediated LINE‐1 de‐repression in macrophages

Abstract

AimTo explore whether hyperglycaemia plays a role in periodontal inflamm‐aging by inducing phenotypical transformation of macrophages, as well as the potential mechanism via SET domain‐bifurcated histone lysine methyltransferase 1 (SETDB1).Materials and MethodsA hyperglycaemic mouse model was established using streptozotocin injection. The alveolar bone was analysed using micro‐computed tomography. Periodontal inflamm‐aging was detected using western blotting, quantitative real‐time PCR and immunohistochemical analysis. In vitro, RAW 264.7 macrophages were incubated with various doses of glucose. siRNA or overexpression plasmids were used to determine the regulatory mechanism of SETDB1 in macrophage senescence and inflamm‐aging under hyperglycaemic conditions. Expression and distribution of SETDB1 and long interspersed element 1 (LINE‐1) in gingival tissues of patients with or without diabetes were detected using immunofluorescent staining.ResultsSETDB1 expression in the periodontal tissues of patients and mice with diabetes was down‐regulated compared with that in non‐diabetic controls. SETDB1 deficiency induced senescence‐like phenotypical changes in macrophages, which aggravated periodontal inflamm‐aging in diabetic mice. Furthermore, metformin treatment rejuvenated SETDB1 activity and alleviated the hyperglycaemia‐induced periodontal inflamm‐aging.ConclusionsThe findings of this study show that SETDB1 regulates senescence‐like phenotypical switching of macrophages and is a potential candidate for the treatment of diabetes‐induced periodontal inflamm‐aging.

Copper Chelation Therapy Attenuates Periodontitis Inflammation through the Cuproptosis/Autophagy/Lysosome Axis

“…When pathogenic microbes invade periodontal tissues, a vast array of immune cells, such as macrophages, T cells, B cells, and dendritic cells, are recruited [ 14 ]. Macrophages play a crucial role in the destruction of periodontal tissues, where their heightened aggregation and activation lead to tissue lesion [ 15 , 16 , 17 , 18 ]. The buildup of inflammatory agents originating from macrophages in gingival tissues and crevicular fluid is linked to the intensity and advancement of periodontitis, while blocking their release is associated with improved bone resorption and the infiltration of inflammatory cells [ 19 , 20 ].…”