Department of Sports Medicine and Joint Surgery, The People's Hospital of China Medical University, Shenyang, 110016, People's Republic of China.
Research Lab of Translational Medicine, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, People's Republic of China.
Biochem Biophys Res Commun. 2020 Apr 16;524(4):832-838. doi: 10.1016/j.bbrc.2020.02.005. Epub 2020 Feb 7.
Apoptosis of osteoblasts plays a crucial role in osteomyelitis. Hydrogen sulfide (HS) levels are increased in the pathophysiological processes of osteomyelitis. However, the effect of HS on the apoptosis of osteoblasts remains unclear. To investigate the specific role of HS in osteoblast apoptosis, MC3T3-E1 and hFOB cells were treated with NaHS or NaS, a donor of HS, and lipopolysaccharide (LPS), during osteomyelitis. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, flow cytometry analysis, western blotting, immunofluorescence, polymerase chain reaction, and Alizarin red staining were performed to examine the effects of HS on osteoblast cell apoptosis, cell osteogenic differentiation, and AKT kinase (AKT)/nuclear factor kappa B (NF-κB) signaling. Hydrogen sulfide increased cell apoptosis, and inhibited the proliferation and osteogenic differentiation of osteoblast cells impaired by LPS. HS increased apoptosis through upregulation of the FAS ligand (FASL) signaling pathway. HS-induced apoptosis was alleviated using a FAS/FASL signaling pathway inhibitor. Treatment with NaHS also increased cell apoptosis by downregulating AKT/NF-κB signaling. In addition, treatment with an AKT signaling pathway activator decreased apoptosis and reversed the inhibitory effects of HS on osteogenic differentiation. Hydrogen sulfide promotes LPS-induced apoptosis of osteoblast cells by inhibiting AKT/NF-κB signaling.
成骨细胞凋亡在骨髓炎中起着至关重要的作用。在骨髓炎的病理生理过程中，硫化氢（HS）水平升高。然而，HS 对成骨细胞凋亡的影响尚不清楚。为了研究 HS 在成骨细胞凋亡中的具体作用，在骨髓炎条件下用 NaHS 或 HS 的供体 NaS 处理 MC3T3-E1 和 hFOB 细胞以及脂多糖（LPS）。采用 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐法、流式细胞术分析、western blot、免疫荧光、聚合酶链反应和茜素红染色检测 HS 对成骨细胞凋亡、细胞成骨分化和 AKT 激酶（AKT）/核因子 kappa B（NF-κB）信号的影响。HS 增加细胞凋亡，并抑制 LPS 损伤的成骨细胞的增殖和成骨分化。HS 通过上调 Fas 配体（FASL）信号通路增加细胞凋亡。使用 Fas/FasL 信号通路抑制剂可减轻 HS 诱导的细胞凋亡。用 NaHS 处理还通过下调 AKT/NF-κB 信号来增加细胞凋亡。此外，AKT 信号通路激活剂的处理可减少细胞凋亡并逆转 HS 对成骨分化的抑制作用。硫化氢通过抑制 AKT/NF-κB 信号促进 LPS 诱导的成骨细胞凋亡。
