Photobiomodulation therapy reduces diabetic periodontal damage through modulation of macrophage metabolism and functions

Diabetes mellitus disrupts macrophage function and immune homoeostasis, thereby increasing susceptibility toward periodontitis. PBMT shows emerging potential in oral rehabilitation. However, it remains underexplored for targeting diabetes-associated periodontal complications. This study aimed to investigate the biomodulatory effects of PBMT on hyperglycaemia-associated macrophage dysfunction, metabolic disorders, and periodontal tissue impairment. Immortalized bone marrow-derived macrophages undergoing glucose transition and streptozotocin-induced diabetic mice received PBMT (980 nm, 3 J/cm²), insulin, or combined therapy. Pharmacological inhibition using specific inhibitors targeting FOXO1, AKT, and ERK was employed to elucidate signaling mechanisms. Cellular functions were assessed through Transwell migration, phagocytosis, and senescence-associated β-galactosidase staining. Metabolic parameters were evaluated via western blotting, ATP/LDH assays, and immunostaining. Tissue morphology was analyzed using micro-CT and H&E staining. PBMT enhanced macrophage phagocytosis, migration, and anti-inflammatory phenotype. The combined PBMT-insulin therapy demonstrated superior efficacy in restoring periodontal architecture compared to monotherapy. Mechanistically, PBMT attenuated FOXO1 hyperactivation primarily through MEK/ERK signaling. PBMT effectively counteracted hyperglycemia-induced metabolic dysregulation, restored macrophage function and phenotype, and mitigated subsequent periodontal tissue damage. The MEK/ERK/FOXO1 signalling pathway may represent a novel mechanism underlying the benefits of PBMT.