• Wen-Jun Wang, Wei Yang, Zhi-Hua Ouyang, Jing-Bo Xue, Xue-Lin Li, Jian Zhang, Wen-Si He, Wen-Kang Chen, Yi-Guo Yan, and Cheng Wang.
• Department of Spine Surgery, The First Affiliated Hospital, University of South China, Hengyang, Hunan 421001, China. Electronic address: wwwwjj167@qq.com.
• Biomed. Pharmacother. 2018 Mar 1; 99: 725-734.

AbstractIntervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. Here, the miRNA microassay assay identified 29 differentially expressed miRNAs in NP tissues from IDD patients compared with healthy controls. Following qRT-PCR validation, miR-21 expression was significantly upregulated in degenerated NP tissues, and showed a positive correlation with disc degeneration grade. Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.Copyright © 2018 Elsevier Masson SAS. All rights reserved.

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