Alpha‐Ketoglutarate Alleviates Systemic Lupus Erythematosus–Associated Periodontitis in a Novel Murine Model

ABSTRACT Aim To establish a reproducible experimental animal model for systemic lupus erythematosus (SLE)‐associated periodontitis (PD), investigate the effects of SLE on PD and assess the therapeutic potential of alpha‐ketoglutarate (αKG) for SLE‐PD treatment. Materials and Methods An SLE‐PD murine model was established via ligature‐induced PD in MRL‐lpr strain, with MRL/MpJ strain as a non‐SLE control. The periodontal state was assessed using micro‐CT, real‐time PCR, histology, immunofluorescence and flow cytometry assays. αKG levels were analysed, and a thermoresponsive gel was designed as a periodontal dimethyl (DM)‐αKG delivery system. αKG levels were analysed in gingival crevicular fluid (GCF) of PD patients with or without SLE. Results SLE significantly increased the periodontal inflammation and bone resorption in the SLE‐PD model. αKG levels in GCF were lower in PD patients with SLE than in PD patients without SLE. Decreased αKG levels in the gingiva and macrophage M1/M2 imbalance were observed in SLE‐PD mice. However, DM‐αKG thermoresponsive gel effectively alleviated the periodontal inflammation, bone resorption and macrophage M1/M2 imbalance in SLE‐PD mice. Conclusions Our study established, for the first time, a novel SLE‐PD murine model and revealed that SLE increases the severity of PD in vivo. Our findings highlight the therapeutic potential of αKG for SLE‐associated PD.