TSPO participates in the pathogenesis of diabetic periodontitis related to mitophagy

Diabetic periodontitis (DP) appears to be the sixth most common complication of diabetes; however, its underlying pathological mechanisms require further explored. Our study investigated the potential function of the translocator protein (TSPO) in the progression of DP, aiming to provide a theoretical foundation for novel treatment strategies.

The ultrastructure and TSPO expression of gingival tissue, collected from healthy individuals, people with periodontitis, and those with DP, were examined. In vivo, a DP model in rats was established using streptozotocin (STZ) and silk ligation. TSPO ligand antagonist PK 11195 was administered as a treatment. Microcomputed tomography (Micro-CT), quantitative real-time polymerase chain reaction (qPCR), histology and immunohistochemistry were employed to assess the destruction, inflammatory and mitophagy in rat periodontal tissues. In in vitro experiments, the inflammatory responses, mitochondrial function, mitophagy and the potential role of TSPO in macrophages were also examined under high-glucose inflammatory conditions, using flow cytometry, fluorescence probes, qPCR, Western blotting and transcription inhibition.

Mitochondrial damage, mitophagy inhibition and increased TSPO expression were observed in gingivae from patients with DP. PK 11195 facilitated the restoration of mitophagy and alleviated the inflammatory destruction of DP rats. Additionally, the high-glucose inflammatory environment intensified the macrophage inflammatory response, ROS production, and mitochondrial damage. These pathological changes were reduced by TSPO inhibition, which could also upregulate the mitophagy.

The inflammation and destruction of periodontal tissue in DP are closely linked to mitophagy associated with TSPO. Immunotherapy targeting TSPO in macrophages could significantly influence the treatment of DP by modulating mitophagy.