title: Drp1-dependent mitochondrial fission mediates osteogenic dysfunction in inflammation through elevated production of reactive oxygen species.
abstract: Although previous studies have implicated pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), to be detrimental for osteogenic activity, the related regulatory mechanisms are not yet fully validated. Since mitochondria host several essential metabolic processes and play a pivotal role in cellular functions, whether and how mitochondrial function contributes to inflammation-induced bone destruction needs further exploration. Our findings revealed that TNF-α impaired osteoblast function, including decreased mRNA levels of osteogenic markers, suppressed ALP expression and activity, and compromised cellular viability. Moreover, increased reactive oxygen species (ROS)-mediated oxidative stress in the TNF-α-treated group enhanced excessive mitochondrial fragmentation and disrupted mitochondrial function. However, treatment with antioxidant N-acetyl cysteine (NAC) or mitochondrial division inhibitor Mdivi-1 protected the cells from these adverse phenomena. These findings provide new insights into the role of the Drp1-dependent mitochondrial pathway in the osteogenic dysfunction during inflammation, indicating that this pathway may be a target for the development of new therapeutic approaches for the prevention and treatment of inflammation-induced bone destruction.
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Xueqi
authors.initials: X
authors.lastname: Gan
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Zhuoli
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Junfei
authors.initials: J
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Oral Disease, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, China.
authors.forename: Haiyang
authors.initials: H
authors.lastname: Yu
mesh_terms: D016475:3T3 Cells; D000111:Acetylcysteine / Q000008:administration & dosage; D000818:Animals; D034281:Dynamins / Q000502:physiology*; D007249:Inflammation / Q000378:metabolism / Q000503:physiopathology*; D051379:Mice; D063154:Mitochondrial Dynamics / Q000502:physiology*; D010012:Osteogenesis / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
chemical_list: D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; C486391:Dnm1l protein, mouse; D034281:Dynamins; D000111:Acetylcysteine