title: MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells.
abstract: The precise role of interleukin-1 beta (IL-1β)-induced extracellular matrix degeneration in the pathogenesis of intervertebral disc degeneration (IDD) is currently unknown. Recent evidence has revealed that microRNAs (miRNAs) are associated with IDD, but their function in the extracellular matrix degradation of nucleus pulposus (NP) tissues is also poorly understood. The aim of this study was to evaluate the expression and functional role of miR-7 in IL-1β-induced disc degeneration. The expression level of miR-7 was investigated in degenerative NP tissues and in IL-1β-induced NP cells using quantitative reverse transcription-polymerase chain reaction amplification analysis. A dual-luciferase reporter assay was then utilized to determine whether growth differentiation factor 5 (GDF5) is a target of miR-7. Finally, mRNA and protein levels of known matrix components and of matrix degradation enzymes were determined to elucidate the function of miR-7 in IL-1β-induced disc degeneration. In this study, we found that miR-7 is highly expressed in human degenerative NP tissues and in IL-1β stimulated NP cells compared to normal controls. We also determined that GDF5 was a target of miR-7. Functional analysis showed that the overexpression of miR-7 significantly enhanced the IL-1β-induced extracellular matrix degeneration, whereas inhibition of miR-7 function by antagomiR-7 prevented NP cell detrimental catabolic changes in response to IL-1β. Additionally, the prevention of IL-1β-induced NP extracellular matrix degeneration by miR-7 silencing was attenuated by GDF5 siRNA. These findings suggest that miR-7 contributes to an impaired ECM in intervertebral discs through targeting GDF5 and miR-7 might therefore represent a novel therapeutic target for the prevention of IDD.
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China; Department of Orthopedics, First Hospital of Wuhan, Zhongshan Road, No.215, Wuhan 430022, China.
authors: Wei
authors: W
authors: Liu
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Yukun
authors: Y
authors: Zhang
authors: Department of Orthopedics, First Hospital of Wuhan, Zhongshan Road, No.215, Wuhan 430022, China.
authors: Ping
authors: P
authors: Xia
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Shuai
authors: S
authors: Li
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Xintong
authors: X
authors: Feng
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Yong
authors: Y
authors: Gao
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Kun
authors: K
authors: Wang
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Yu
authors: Y
authors: Song
authors: Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1106, Boston, MA, 02114, USA.
authors: Zhenfeng
authors: Z
authors: Duan
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Shuhua
authors: S
authors: Yang
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.
authors: Zengwu
authors: Z
authors: Shao
authors: Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China. Electronic address: yangcao1971@sina.com.
authors: Cao
authors: C
authors: Yang
mesh_terms: D000293:Adolescent; D000328:Adult; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D005260:Female; D018390:Gene Targeting / Q000379:methods; D055428:Growth Differentiation Factor 5 / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D053583:Interleukin-1beta / Q000494:pharmacology*; D007403:Intervertebral Disc / Q000187:drug effects / Q000378:metabolism; D055959:Intervertebral Disc Degeneration / Q000235:genetics / Q000378:metabolism*; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D000070614:Nucleus Pulposus / Q000187:drug effects / Q000378:metabolism*; D055815:Young Adult
chemical_list: D055428:Growth Differentiation Factor 5; D053583:Interleukin-1beta; D035683:MicroRNAs; C525893:GDF5 protein, human; C549242:MIRN7-1 microRNA, human
keywords: GDF5; IL-1β; Intervertebral disc degeneration; Nucleus pulposus; miR-7