Department of Orthopedics, The Second Affiliated Hospital, Soochow University, Suzhou, China; Department of Orthopedics, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Orthopedics, The Second Affiliated Hospital, Soochow University, Suzhou, China.
Biochem Biophys Res Commun. 2018 Sep 18;503(4):2255-2262. doi: 10.1016/j.bbrc.2018.06.146. Epub 2018 Jul 3.
Dexamethasone (Dex) can induce injury to human osteoblasts. Long non-coding RNA (LncRNA) EPIC1 (Lnc-EPIC1) is a novel Myc-interacting LncRNA. Its effect on Dex-treated human osteoblasts is studied here. In OB-6 osteoblastic cells and primary human osteoblasts, treatment with Dex increased expression of Lnc-EPIC1. Its expression is also elevated in the necrotic femoral head tissues of Dex-taking patients. Ectopic overexpression of Lnc-EPIC1 inhibited Dex-induced apoptosis and programmed necrosis in OB-6 cells and primary human osteoblasts. Reversely, Lnc-EPIC1 silencing by targeted siRNA potentiated Dex-induced cytotoxicity. Myc is the target of Lnc-EPIC1 in osteoblasts. Exogenous overexpression of Myc protected OB-6 cells from Dex. Conversely, Myc knockout by CRISPR-Cas-9 method abolished Lnc-EPIC1-induced OB-6 cytoprotection against Dex. Together, Lnc-EPIC1 expression protects human osteoblasts from Dex possible via regulation of Myc.
地塞米松（Dex）可诱导人成骨细胞损伤。长链非编码 RNA（LncRNA）EPIC1（Lnc-EPIC1）是一种新型 Myc 相互作用的 LncRNA。本研究探讨了其对 Dex 处理的人成骨细胞的影响。在 OB-6 成骨细胞和原代人成骨细胞中，Dex 处理可增加 Lnc-EPIC1 的表达。在服用 Dex 的患者的坏死股骨头组织中，其表达也升高。Lnc-EPIC1 的异位过表达抑制了 Dex 诱导的 OB-6 细胞和原代人成骨细胞的凋亡和程序性坏死。相反，靶向 siRNA 沉默 Lnc-EPIC1 增强了 Dex 诱导的细胞毒性。Myc 是成骨细胞中 Lnc-EPIC1 的靶标。外源性过表达 Myc 可保护 OB-6 细胞免受 Dex 影响。相反，CRISPR-Cas-9 方法敲除 Myc 可消除 Lnc-EPIC1 诱导的 Dex 对 OB-6 细胞的保护作用。总之，Lnc-EPIC1 的表达可能通过调节 Myc 来保护人成骨细胞免受 Dex 的影响。
