Inhibited microRNA-494-5p promotes proliferation and suppresses senescence of nucleus pulposus cells in mice with intervertebral disc degeneration by elevating TIMP3
Authors: Gang Chen
Zhengkuan Xu
Xiaopeng Zhou
Hao Li
Journal: Cell Cycle (2021)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: Intervertebral disc degeneration; MicroRNA-494-5p; cellular senescence; differentiation; nucleus pulposus cells
Affiliations: Orthopedic Department, The Second Affiliated Hospital Zhejiang University School of Medicine , Hangzhou, Zhejiang, China.

Abstract:  It has been unraveled that microRNAs (miRNAs) played crucial roles in processes of human diseases, while the role of miR-494-5p in intervertebral disc degeneration (IDD) remains scarcely studied. We aimed to investigate the mechanisms of miR-494-5p in IDD with the involvement of tissue inhibitor of metalloproteinase 3 (TIMP3). Expression of miR-494-5p and TIMP3 in IDD clinical specimens was assessed. The IDD models were established by needle punching, which were then injected with low expression of miR-494-5p or TIMP3 overexpression lentivirus to observe their effects on pathology and apoptosis in IDD mice. The nucleus pulposus cells were isolated and, respectively, treated with miR-494-5p inhibitor or TIMP3 overexpression plasmid to determine the viability, apoptosis, and senescence in vitro. Furthermore, the expression of Aggrecan, Col-2, Caveolin-1, and SA-β-gal in nucleus pulposus cells in vitro were measured. The target relation between miR-494-5p and TIMP3 was determined. An increased expression of miR-494-5p and a decreased expression of TIMP3 were found in IDD. Downregulation of miR-494-5p or overexpression of TIMP3 could relieve pathology and suppress nucleus pulposus cell apoptosis in IDD mice, as well as promote the viability and attenuate the apoptosis and senescence of nucleus pulposus cells from IDD mice. Moreover, inhibition of miR-494-5p or overexpression of TIMP3 upregulated Aggrecan and Col-2 expression while downregulated Caveolin-1 and SA-β-gal expression, and TIMP3 was the target gene of miR-494-5p. Results of this study indicated that the degradation of miR-494-5p ameliorates the development of IDD by elevating TIPM3, which may provide new targets for IDD treatment. 

Retracted: Yes

PubPeer comments:
 Fig 5b,  cell cycle distribution of transfected miceu2019 nucleus pulposus cells in each group was assessed by flow cytometry . The non-zigzag solid line in each panel (e.g. orange arrow) is supposed to be the sum of the red and striped humps. Clearly it is not. These flow-cytometry results appear to be hand-drawn. ![file] , 
 Retracted [17 March 2022] . ------------------------------ We, the Editors and Publisher of the journal *Cell Cycle*, have retracted the following article: Gang Chen, Xiaopeng Zhou, Hao Li, and Zhengkuan Xu. Inhibited microRNA-494-5p promotes proliferation and suppresses senescence of nucleus pulposus cells in mice with intervertebral disc degeneration by elevating TIMP3. Cell Cycle. 2021;20(1):11-22. doi: 10.1080 15384101.2020.1843812. Since publication, significant concerns have been raised about the integrity of the data and reported results in the article. When approached for an explanation, the authors did not provide their original data or any necessary supporting information. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as u2018Retractedu2019. ,