Inhibition of microRNA-384-5p alleviates osteoarthritis through its effects on inhibiting apoptosis of cartilage cells via the NF-κB signaling pathway by targeting SOX9
Authors: Weikai Zhang
Hui Huang
Weihua Hu
Fengjing Guo
Weifeng Yin
Peng Cheng
Anmin Chen
Journal: Cancer Gene Therapy (2018)
Discipline: CLINICAL MEDICINE
Keywords: Osteoarthritis; microRNA-384-5p; SOX9; cartilage cells; proliferation
Affiliations: Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R. China., Department of Orthopaedic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, P.R. China. .

Abstract:  Osteoarthritis (OA), a major cause of pain and disability, is a serious public issue worldwide. Some microRNAs (miRNAs) and SOX9 have been found to be expressed in OA. Therefore, the aim of this study is to investigate effects of microRNA-384-5p (miR-384-5p) on cartilage cell proliferation and apoptosis in mice with OA by targeting SOX9 through the NF-κB signaling pathway. First, bioinformatics was used to predict the SOX9-mediated miRNA (miR-384-5p), and dual luciferase reporter gene assay was conducted to further verify the relationship between miR-384-5p and SOX9. Then, the expression of miR-384-5p, SOX9, and NF-kB in mice modeled with OA was detected. To investigate the specific mechanism of miR-384-5p in OA, mimic and inhibitor of miR-384-5p and siRNA against SOX9 were used to transfect cartilage cells. Finally, proliferation, cell cycle, and cell apoptosis were detected using MTT assay and flow cytometry, respectively. Our results indicated that OA mice exhibited decreased expression of SOX9 and NF-kB but higher miR-384-5p expression. In addition, over-expressed miR-384-5p or silenced SOX9 could inhibit cell proliferation, and block cell cycle entry and induces apoptosis. SOX9 was a target gene of miR-384-5p. The NF-kB signaling pathway was inactivated after overexpression of miR-384-5p. Furthermore, we also observed that the effect of miR-384-5p inhibition was rescued when SOX9 was knocked down. The results support the view that inhibition of miR-384-5p could impede apoptosis and promote proliferation of cartilage cells through activating the NF-κB signaling pathway by promoting SOX9, thereby preventing the development of OA. 

Retracted: No

PubPeer comments:
 This paper figures on the list of  The best of Cancer Gene Therapy 2018-2019 . Figure 8A: The flow cytometry data have been manipulated. Figure 6B and Figure 9B: Western blots have been duplicated manipulated. ![file] ![file] , 
 I came here with similar concerns about Figure 6, 8, and 9. Here is how I had marked Figure 8A, with some additional findings. ![file] , 
 Similarities of the Western blot bands in Figures 6 and 9 to those in Xian-Qun Chu et al., doi: 10.1016 j.prp.2017.10.003 , https: pubpeer.com publications F1C998AB3F11B5907DE5C45822EE5E: ![file] ![file] , 
 Many other permutations of the Western Blots and the flow-cytometry were discussed in a blogpost: https: forbetterscience.com 2020 08 12 we-are-extremely-guilty-and-distressed For more up-to-date though eccentrically-organised results, this spreadsheet may be of interest: https: docs.google.com spreadsheets d 1r0MyIYpagBc58BRF9c3luWNlCX8VUvUuPyYYXzxWvgY edit?usp=sharing For instance, the Flow cytometry column has entries for beavers (short for beavers begging the clouds to rain ), linking to PP threads for [Yu et al (2019)] , [Wang et al (2018)] , and [Wu et al (2018)] . The flow-cytometry figures from those papers are ![] ![] ![] Whether  The flow cytometry data have been manipulated , as asserted in #1, they have certainly been widely disseminated. , 
 Correction published: [29 July 2020] .  The original version of this Article contained inaccuracies in Fig. 6b (u201cSox9u201d band) and Fig. 8a (u201cmir-384-5p inhibitoru201d and u201c8 mir-384-5p inhibitor + sirna-sox9u201d groups). Both figures have been corrected in both the PDF and HTML versions of the Article. ![file] ![file] We are left wondering why the replacement panels in Fig 8a have such different resolution from the unaltered panels; or why those unaltered panels are so similar to ones in papers from unrelated teams of authors. ![file] , 
 Most of the primers presented in Table 1 appear to be incorrect (NCBI nucleotide blast with filter for Mus musculus). ![file] ,