TNF-α is upregulated in T2DM patients with fracture and promotes the apoptosis of osteoblast cells in vitro in the presence of high glucose

Fracture healing is regulated by proinflammatory mediators such as tumor necrosis factor-alpha (TNF-alpha), which poses influence on the balance between bone formation and remodeling. And the diabetes is thought to contribute to the delayed diabetic fracture healing. In the present study, we examined the promotion to proinflammatory cytokines and chemokines in type 2 diabetes mellitus (T2DM) patients with bone fractures, and then evaluated the promotion to TNF-alpha by the high glucose treatment in human osteoblast-like MG-63 cells and the regulatory role of the promoted TNF-alpha on the MG-63 cell apoptosis. It was demonstrated that there were significantly-upregulated high-sensitivity C-reactive protein (hsCRP) TNF-alpha, IL-1 beta, IL-6, IFN-gamma-inducible protein 10 (IP-10) and RANTES in T2DM patients with bone fracture. And the promotion to INF-alpha and IL-1 beta was confirmed in vitro in both mRNA and protein levels in high glucose-treated MG-63 cells. And either TNF-alpha or high glucose reduced the viability of MG-63 cells, promoted apoptosis and upregulated apoptosis-associated markers, such as released cytochrome c, cleaved caspase 3 and lyzed PARP. Moreover, there was a synergistic effect between TNF-alpha and high glucose. The viability reduction and the apoptosis induction of MG-63 cells were significantly higher in the group with both TNF-alpha and high glucose treatments, than in the group with singular TNF-alpha treatment. In conclusion, our study demonstrated that proinflammatory cytokines and chemokines were promoted in T2DM patients with bone fracture or in osteoblasts by the high glucose stimulation. TNF-alpha and high glucose synergistically reduced the viability and induced the apoptosis in the osteoblast-like MG-63 cells in vitro. It implies the significant regulatory role of TNF-alpha in the delayed fracture healing in T2DM. (C) 2016 Elsevier Ltd. All rights reserved.