Drp1-dependent mitochondrial fission mediates osteogenic dysfunction in inflammation through elevated production of reactive oxygen species

• DOI: 10.1371/journal.pone.0175262
• Publication Date: 2017-04-07T14:07:12Z
• Authors: Ling Zhang; Xueqi Gan; Yuting He; Zhuoli Zhu; Junfei Zhu; Haiyang Yu
• Keywords: Mitochondrial ROS; Fragmentation

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 play a pivotal role in cellular functions, whether how mitochondrial function contributes inflammation-induced bone destruction needs further exploration. Our findings revealed that TNF-α impaired osteoblast function, including decreased mRNA levels of markers, suppressed ALP expression compromised viability. Moreover, increased reactive oxygen species (ROS)-mediated oxidative stress TNF-α-treated group enhanced excessive fragmentation disrupted function. However, treatment with antioxidant N-acetyl cysteine (NAC) or division inhibitor Mdivi-1 protected cells from these adverse phenomena. These provide new insights into Drp1-dependent pathway dysfunction during inflammation, indicating this may target development therapeutic approaches prevention destruction.