机构：[a]Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong,[b]Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing,[c]Department of Orthopedics, the Second Affiliated Hospital of Suzhou University, Suzhou, China
Background/Aims: Dexamethasone (Dex) induces injuries to human osteoblasts. In this study, we tested the potential role of the long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (Lnc-MALAT1) in this process. Materials: Two established human osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts were treated with Dex. Lnc-MALAT1 expression was analyzed by quantitative real-time polymerase chain reaction assay. Cell viability, apoptosis, and death were tested by the MTT assay, histone-DNA assay, and trypan blue staining assay, respectively. AMP-activated protein kinase (AMPK) signaling was evaluated by western blotting and AMPK activity assay. Results: Lnc-MALAT1 expression was downregulated by Dex treatment in the established osteoblastic cell lines (OB-6 and hFOB1.19) and primary human osteoblasts. The level of Lnc-MALAT1 was decreased in the necrotic femoral head tissues of Dex-administered patients. In osteoblastic cells and primary human osteoblasts, forced overexpression of Lnc-MALAT1 using a lentiviral vector (LV-MALAT1) inhibited Dex-induced cell viability reduction, cell death, and apoptosis. Conversely, transfection with Lnc-MALAT1 small interfering RNA aggravated Dex-induced cytotoxicity. Transfection with LV-MALAT1 downregulated Ppm1e (protein phosphatase, Mg2+/ Mn2+-dependent 1e) expression to activate AMPK signaling. Treatment of osteoblasts with AMPK1 short hairpin RNA or dominant negative mutation (T172A) abolished LV-MALAT1-induced protection against Dex-induced cytotoxicity. Furthermore, LV-MALAT1 induced an increase in nicotinamide adenine dinucleotide phosphate activity and activation of Nrf2 signaling. Dex-induced reactive oxygen species production was significantly attenuated by LV-MALAT1 transfection in osteoblastic cells and primary osteoblasts. Conclusion: Lnc-MALAT1 protects human osteoblasts from Dex-induced injuries, possibly via activation of Ppm1e-AMPK signaling.
基金：
This work was generously supported by grants from the National Natural Science
Foundation of China (81501866), Jiangsu Provincial Young Medical Talent Foundation
(QNRC2016411), the Science and Technology Program of Nantong (MS22015051), and
Nantong 226 High-level Talents Project and Jiangsu 333 Talent Peak Program (To J. F.).
第一作者机构：[a]Department of Orthopaedics, The Second Affiliated Hospital of Nantong University, Nantong,[b]Department of Orthopaedics, Jinling Hospital, Nanjing Medical University, Nanjing,
共同第一作者：
通讯作者：
通讯机构：[*1]Department of Orthopaedics, the Second Affiliated Hospital of Nantong University, North Hai-er-xiang Road 6, Nantong, Jiangsu 226001 (China)
推荐引用方式(GB/T 7714)：
Jian-bo Fan,Yingzi Zhang,Wei Liu,et al.Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling[J].CELLULAR PHYSIOLOGY AND BIOCHEMISTRY.2018,51(1):31-45.doi:10.1159/000495159.
APA：
Jian-bo Fan,Yingzi Zhang,Wei Liu,Xin-hui Zhu,Da-wei Xu...&Zhi-ming Cui.(2018).Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling.CELLULAR PHYSIOLOGY AND BIOCHEMISTRY,51,(1)
MLA：
Jian-bo Fan,et al."Long Non-Coding RNA MALAT1 Protects Human Osteoblasts from Dexamethasone-Induced Injury via Activation of PPM1E-AMPK Signaling".CELLULAR PHYSIOLOGY AND BIOCHEMISTRY 51..1(2018):31-45
