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MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells.
Biomed Pharmacother. 2016 Oct; 83:1414-1421.BP

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+Show Affiliations

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.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.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Sarcoma Biology Laboratory, Center for Sarcoma and Connective Tissue Oncology, Massachusetts General Hospital, 100 Blossom St., Jackson 1106, Boston, MA, 02114, USA.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Jiefang Road, No. 1277,Wuhan 430022, China.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

27583982

Citation

Liu, Wei, et al. "MicroRNA-7 Regulates IL-1β-induced Extracellular Matrix Degeneration By Targeting GDF5 in Human Nucleus Pulposus Cells." Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, vol. 83, 2016, pp. 1414-1421.
Liu W, Zhang Y, Xia P, et al. MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. Biomed Pharmacother. 2016;83:1414-1421.
Liu, W., Zhang, Y., Xia, P., Li, S., Feng, X., Gao, Y., Wang, K., Song, Y., Duan, Z., Yang, S., Shao, Z., & Yang, C. (2016). MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie, 83, 1414-1421. https://doi.org/10.1016/j.biopha.2016.08.062
Liu W, et al. MicroRNA-7 Regulates IL-1β-induced Extracellular Matrix Degeneration By Targeting GDF5 in Human Nucleus Pulposus Cells. Biomed Pharmacother. 2016;83:1414-1421. PubMed PMID: 27583982.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - MicroRNA-7 regulates IL-1β-induced extracellular matrix degeneration by targeting GDF5 in human nucleus pulposus cells. AU - Liu,Wei, AU - Zhang,Yukun, AU - Xia,Ping, AU - Li,Shuai, AU - Feng,Xintong, AU - Gao,Yong, AU - Wang,Kun, AU - Song,Yu, AU - Duan,Zhenfeng, AU - Yang,Shuhua, AU - Shao,Zengwu, AU - Yang,Cao, Y1 - 2016/08/30/ PY - 2016/06/03/received PY - 2016/08/01/revised PY - 2016/08/25/accepted PY - 2016/10/25/pubmed PY - 2017/2/7/medline PY - 2016/9/2/entrez KW - GDF5 KW - IL-1β KW - Intervertebral disc degeneration KW - Nucleus pulposus KW - miR-7 SP - 1414 EP - 1421 JF - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie JO - Biomed. Pharmacother. VL - 83 N2 - 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. SN - 1950-6007 UR - https://www.unboundmedicine.com/medline/citation/27583982/MicroRNA_7_regulates_IL_1β_induced_extracellular_matrix_degeneration_by_targeting_GDF5_in_human_nucleus_pulposus_cells_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0753-3322(16)30802-2 DB - PRIME DP - Unbound Medicine ER -