NLRP3 inflammasome inhibitor glyburide expedites diabetic-induced impaired fracture healing.

Abstract

Localized inflammation is accompanied by the diabetic-induced fracture. The present study aims to investigate the therapeutic effects of glyburide, an NLRP3 inflammasome inhibitor, in a diabetic-induced fracture model. An animal model of diabetic-induced fracture was established and the mice were administrated with metformin or glyburide for 3 weeks. Quantitative polymerase chain reaction (qPCR) and Western blotting were used to evaluate the relative expressions of IFN-γ, TNF-α, and IL-6. Micro-computed tomography (μCT) scanning was applied to evaluate bone callus formation. Histopathology examinations of fractured femur sections were performed using Tartrate-resistant acid phosphatase (TRAP) staining and Alcian blue and orange G staining. Bone strength was evaluated using Torsional testing. Our results showed that treatment of glyburide significantly decreased the expressions of IFN-γ, TNF-α, and IL-6 in the fracture calluses in diabetic-induced fracture model, while bone callus volume and bone volume fraction were increased. Additionally, our results also demonstrated that treatment of glyburide rescued the increase of osteoclasts in the bone-cartilage interface. Apart from decreasing a percentage of cartilage area and increasing the percentage of bone and fibrotic tissue area, treatment of glyburide increased the maximum torque and yield torque of fractures. These results implied that glyburide might be used as a potential drug candidate for diabetic-induced fracture.