Oncotarget

Research Papers:

Inflammatory microRNA-194 and -515 attenuate the biosynthesis of chondroitin sulfate during human intervertebral disc degeneration

Bo Hu, Chen Xu, Ye Tian, Changgui Shi, Ying Zhang, Lianfu Deng, Hongyu Zhou, Peng Cao, Huajiang Chen _ and Wen Yuan

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:49303-49317. https://doi.org/10.18632/oncotarget.17571

Metrics: PDF 1112 views  |   HTML 1483 views  |   ?  


Abstract

Bo Hu1,*, Chen Xu1,*, Ye Tian1,*, Changgui Shi1, Ying Zhang1, Lianfu Deng2, Hongyu Zhou1, Peng Cao1, Huajiang Chen1 and Wen Yuan1

1Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China

2Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

*These authors contributed equally to this work

Correspondence to:

Huajiang Chen, email: spine.chen@163.com

Wen Yuan, email: yuanwenspine@126.com

Peng Cao, email: mdpinocao@gmail.com

Keywords: intervertebral disc degeneration, nucleus pulposus, chondroitin sulfate, biosynthesis, glycosyltransferases

Received: May 31, 2016     Accepted: April 17, 2017     Published: May 02, 2017

ABSTRACT

Intervertebral disc degeneration (IDD) is characterized by dehydration and loss of extracellular matrixes in the nucleus pulposus region. Chondroitin sulfate has been found to be the water-binding molecule that played a key role in IDD. Although investigators have reported that inflammatory cytokines are involved in the reduction of chondroitin sulfate in IDD, but the underlying mechanism is unrevealed. Since chondroitin sulfate synthesis is controlled by chondroitin sulfate glycosyltransferases CHSY-1/2/3 and CSGALNACT-1/2, their functional role and regulatory mechanism in IDD is not fully studied. Here, we set out to investigate the function and regulatory roles of these factors during IDD development. We found that among these chondroitin sulfate glycosyltransferases, CHSY-1/2/3 are significantly down-regulated in severe IDD samples than mild IDD samples. In vitro experiments revealed that Interleukin-1β and Tumor Necrosis Factor-α stimulation led to significant reduction of CHSY-1/2/3 at protein level than mRNA level in NP cells, indicating a post-transcriptional regulatory mechanisms are involved. By computational prediction and analysis, we found that inflammatory cytokines stimulated microRNA-194 and -515 target CHSY-1/2/3 mRNA and significantly interrupt their translation and downstream chondroitin sulfate deposition. Inhibition of microRNA-194 and -515 however, significantly rescued CHSY-1/2/3 expressions and chondroitin sulfate deposition. These findings together demonstrated a vital role of inflammatory stimulated microRNAs in promoting intervertebral disc degeneration by interrupt chondroitin sulfate synthesis, which may provide new insights into the mechanism and therapeutic approaches in IDD.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 17571