Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration (IDD). However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, which was transcribed in the opposite direction to ADAMTS5. In the present study, through mining computational algorithm programs, and publicly available data sets, we identified Ras-responsive element-binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells. RNA pull-down, RNA immunoprecipitation (RIP), in vitro binding assays, and gain- and loss-of-function studies indicated that a physical interaction between linc-ADAMTS5 and splicing factor proline/glutamine-rich (SFPQ) facilitated the recruitment of RREB1 to binding sites within the ADAMTS5 promoter to induce chromatin remodeling. This resulted in subdued ADAMTS5 levels in cultured NP cells involving histone deacetylases (HDACs). In clinical NP tissues, linc-ADAMTS5 and RREB1 were correlated negatively with ADAMTS5 expression. Taken together, these results demonstrate that RREB1 cooperates with noncoding RNA linc-ADAMTS5 to inhibit ADAMTS5 expression, thereby affecting degeneration of the extracellular matrix (ECM) of the intervertebral disc (IVD).
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Image demonstrates the ultrastructural cortical basement membrane changes in SHRSP brain: accumulation of lipofuscin in pericytes. For further details, see article by Screiber et al in this issue (pages 1001–1013). Image kindly provided by Stefanie Schreiber.
Research Article|
May 04 2017
The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression
Kun Wang;
Kun Wang
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Yu Song;
Yu Song
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wei Liu;
Wei Liu
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
2Department of Orthopedics, First Hospital of Wuhan, Wuhan, China
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Xinghuo Wu;
Xinghuo Wu
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Yukun Zhang;
Yukun Zhang
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Shuai Li;
Shuai Li
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Liang Kang;
Liang Kang
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Ji Tu;
Ji Tu
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Kangcheng Zhao;
Kangcheng Zhao
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Wenbin Hua;
Wenbin Hua
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Cao Yang
1Department of Orthopedics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Correspondence: Cao Yang ([email protected])
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Publisher: Portland Press Ltd
Received:
November 28 2016
Revision Received:
March 16 2017
Accepted:
March 24 2017
Accepted Manuscript online:
March 24 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2017 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society
2017
Clin Sci (Lond) (2017) 131 (10): 965–979.
Article history
Received:
November 28 2016
Revision Received:
March 16 2017
Accepted:
March 24 2017
Accepted Manuscript online:
March 24 2017
Citation
Kun Wang, Yu Song, Wei Liu, Xinghuo Wu, Yukun Zhang, Shuai Li, Liang Kang, Ji Tu, Kangcheng Zhao, Wenbin Hua, Cao Yang; The noncoding RNA linc-ADAMTS5 cooperates with RREB1 to protect from intervertebral disc degeneration through inhibiting ADAMTS5 expression. Clin Sci (Lond) 1 May 2017; 131 (10): 965–979. doi: https://doi.org/10.1042/CS20160918
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