机构：[1]The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China[2]The Department of Orthopedics, The Second Affiliated Hospital of Soochow University, Suzhou 215000, China[3]The Center of Diagnosis and Treatment for Childrens’ Bone Disease, Childrens’ Hospital Affiliated to Soochow University, Suzhou 215000, Jiangsu, PR China[4]Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing 210008, Jiangsu, PR China
Activation of AMP-activated protein kinase (AMPK) could potently protect osteoblasts/osteoblastic cells from dexamethasone (Dex). We aim to induce AMPK activation via microRNA ("miRNA") downregulation of its phosphatase Ppm1e. We discovered that microRNA-135b ("miR-135b") targets the 3' untranslated regions (UTRs) of Ppm1e. In human osteoblasticOB-6 cells and hFOB1.19 cells, forced-expression of miR-135b downregulated Ppm1e and activated AMPK signaling. miR-135b also protected osteoblastic cells from Dex. shRNA-induced knockdown of Ppm1e similarly activated AMPK and inhibited Dex-induced damages. Intriguingly, in the Ppm1e-silenced osteoblastic cells, miR-135b expression failed to offer further cytoprotection against Dex. Notably, AMPK knockdown (via shRNA) or dominant negative mutation abolished miR-135b-induced AMPK activation and cytoprotection against Dex. Molecularly, miR-135b, via activating AMPK, increased nicotinamide adenine dinucleotide phosphate (NADPH) activity and inhibited Dex-induced oxidative stress. At last, we found that miR-135b level was increased in human necrotic femoral head tissues, which was correlated with Ppm1e downregulation and AMPK activation. There results suggest that miR-135b expression downregulates Ppm1e to activate AMPK signaling, which protects osteoblastic cells from Dex.
基金：
This work was generously supported by grants from the National Natural Science Foundation of China (81501866), and the Science and Technology Program of Nantong (MS22015051).
第一作者机构：[1]The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China[4]Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing 210008, Jiangsu, PR China
共同第一作者：
通讯作者：
通讯机构：[1]The Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, PR China
推荐引用方式(GB/T 7714)：
Jian-Bo Fan,Jian-Wei Ruan,Wei Liu,et al.miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone[J].ONCOTARGET.2016,7(43):70613-70622.doi:10.18632/oncotarget.12138.
APA：
Jian-Bo Fan,Jian-Wei Ruan,Wei Liu,Lun-Qing Zhu,Xin-Hui Zhu...&Zhi-Ming Cui.(2016).miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone.ONCOTARGET,7,(43)
MLA：
Jian-Bo Fan,et al."miR-135b expression downregulates Ppm1e to activate AMPK signaling and protect osteoblastic cells from dexamethasone".ONCOTARGET 7..43(2016):70613-70622
医学