机构：[1]Department of Orthopaedics, Peking Union Medical College Hospital, Beijing, China.[2]Department of Orthopaedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.[3]The Center of Diagnosis and Treatment for Children’s Bone Diseases, The Children’s Hospital of Soochow University, Suzhou, China.[4]Spinal Surgery, Sino-Japanese Friendship Hospital, Beijing, China
Activation of nuclear-factor-E2-related factor 2 (Nrf2) cascade can alleviate dexamethasone (DEX)-induced oxidative injury and death of human osteoblasts. A recent study has shown that phosphoglycerate kinase 1 (PGK1) inhibition/depletion will lead to Kelch-like ECH-associated protein 1 (Keap1) methylglyoxal modification, thereby activating Nrf2 signaling cascade. Here, in OB-6 osteoblastic cells and primary human osteoblasts, PGK1 silencing, by targeted shRNA, induced Nrf2 signaling cascade activation, causing Nrf2 protein stabilization and nuclear translocation, as well as increased expression of ARE-dependent genes (HO1, NQO1, and GCLC). Functional studies demonstrated that PGK1 shRNA largely attenuated DEX-induced oxidative injury and following death of OB-6 cells and primary osteoblasts. Furthermore, PGK1 knockout, by the CRISPR/Cas9 method, similarly induced Nrf2 signaling activation and protected osteoblasts from DEX. Importantly, PGK1 depletion-induced osteoblast cytoprotection against DEX was almost abolished by Nrf2 shRNA. In addition, Keap1 shRNA mimicked and nullified PGK1 shRNA-induced anti-DEX osteoblast cytoprotection. At last we show that PGK1 expression is downregulated in human necrotic femoral head tissues of DEX-taking patients, correlating with HO1 depletion. Collectively, these results show that PGK1 depletion protects human osteoblasts from DEX via activation of Keap1-Nrf2 signaling cascade.
基金：
Basic Research Program of Jiangsu Province; Social Development Project of Jiangsu Science and Technology Department [BE2016674]
第一作者机构：[1]Department of Orthopaedics, Peking Union Medical College Hospital, Beijing, China.
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Liang Jinqian,Zhang XiangYang,Zhen YunFang,et al.PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone[J].CELL DEATH & DISEASE.2019,10:doi:10.1038/s41419-019-2112-1.
APA：
Liang, Jinqian,Zhang, XiangYang,Zhen, YunFang,Chen, Chong,Tan, Haining...&Tan, MingSheng.(2019).PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone.CELL DEATH & DISEASE,10,
MLA：
Liang, Jinqian,et al."PGK1 depletion activates Nrf2 signaling to protect human osteoblasts from dexamethasone".CELL DEATH & DISEASE 10.(2019)
生物学