title: TNF-α is upregulated in T2DM patients with fracture and promotes the apoptosis of osteoblast cells in vitro in the presence of high glucose.
abstract: Fracture healing is regulated by proinflammatory mediators such as tumor necrosis factor-α (TNF-α), 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-α by the high glucose treatment in human osteoblast-like MG-63 cells and the regulatory role of the promoted TNF-α on the MG-63 cell apoptosis. It was demonstrated that there were significantly-upregulated high-sensitivity C-reactive protein (hsCRP) TNF-α, IL-1β, IL-6, IFN-γ-inducible protein 10 (IP-10) and RANTES in T2DM patients with bone fracture. And the promotion to TNF-α and IL-1β was confirmed in vitro in both mRNA and protein levels in high glucose-treated MG-63 cells. And either TNF-α 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-α and high glucose. The viability reduction and the apoptosis induction of MG-63 cells were significantly higher in the group with both TNF-α and high glucose treatments, than in the group with singular TNF-α 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-α 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-α in the delayed fracture healing in T2DM.
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Mingqi
authors.initials: M
authors.lastname: Sun
authors.affiliation: Medical Examination Center, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010010, China.
authors.forename: Junli
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Orthopedics and Trauma, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics and Trauma, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Hao
authors.affiliation: Department of Orthopaedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. Electronic address: dianmigjiang@163.com.
authors.forename: Dianming
authors.initials: D
authors.lastname: Jiang
authors.affiliation: Department of Orthopedics and Trauma, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China. Electronic address: guoneyubao@163.com.
authors.forename: Guoyu
authors.initials: G
authors.lastname: Bao
authors.affiliation: Department of Orthopedics and Trauma, The Second Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010030, China.
authors.forename: Guanghui
authors.initials: G
authors.lastname: Liu
mesh_terms: D000368:Aged; D017209:Apoptosis / Q000235:genetics; D001842:Bone and Bones / Q000473:pathology; D002097:C-Reactive Protein / Q000235:genetics; D053148:Caspase 3 / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival; D018925:Chemokines / Q000097:blood; D045304:Cytochromes c / Q000235:genetics; D016207:Cytokines / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000276:immunology* / Q000503:physiopathology; D005260:Female; D017102:Fracture Healing / Q000187:drug effects / Q000276:immunology; D050723:Fractures, Bone / Q000276:immunology* / Q000503:physiopathology; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000097:blood / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010006:Osteoblasts / Q000187:drug effects* / Q000276:immunology / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics* / Q000276:immunology; D015854:Up-Regulation
chemical_list: D018925:Chemokines; D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D002097:C-Reactive Protein; D045304:Cytochromes c; D053148:Caspase 3; D005947:Glucose
keywords: Apoptosis; Bone fracture; High glucose; Osteoblast cells; T2DM; TNF-α