Abstract
Osteoarthritis (OA) is one of the most prevalent musculoskeletal diseases globally, leading to chronic disability and poor prognosis. One of the approaches for optimizing OA treatment is to find early effective diagnostic biomarkers. The contribution of microRNAs (miRNAs) in OA progression is now being increasingly recognized. This review provides a comprehensive summary on studies reporting the expression profiling of miRNAs in OA and associated signaling pathways. We performed a systematic search of the Embase, Web of Science, PubMed, and Cochrane library databases. This systematic review is reported according to the PRISMA checklist. Studies which identified miRNAs with aberrant expression compared to controls during OA progression were included, and a meta-analysis was performed. Results from the random effects model were provided as log10 odds ratios (logORs) and 95% confidence intervals. Sensitivity analysis was conducted to confirm the accuracy of the results. Subgroup analysis was conducted based on tissue source. The target genes of miRNAs identified in this study were extracted from the MiRWalk database, and these target genes were enriched in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. A total of 191 studies reporting 162 miRNAs were included in our meta-analysis. Among them, 36 miRNAs distributed across 96 studies were expressed in the same direction in at least two studies (13 up-regulated and 23 down-regulated). Subgroup analysis of tissue source revealed that the highest number of studies was conducted using articular cartilage, where the most up-regulated miRNAs were miR-146a-5p (logOR 7.355; P < 0.001) and miR-34a-5p (logOR 6.955; P < 0.001), and the most down-regulated miRNAs were miR-127-5p (logOR 6.586; P < 0.001) and miR-140-5p (logOR 6.373; P < 0.001). Enrichment analysis of 752 downstream target genes of all identified miRNAs was performed, and the regulatory relationships among them were displayed. Mesenchymal stem cells and transforming growth factor-β were found to be the most important downstream effectors regulated by miRNA in OA. This study highlighted the importance of miRNA signaling in OA progression and identified a number of prominent miRNAs including miR-146a-5p, miR-34a-5p, miR-127-5p, and miR-140-5p which might be considered as potential biomarkers for OA.
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Data availability
The guarantor (BW) is willing to examine all requests for the full dataset after a period of two years from the date of this publication. The corresponding author should be contacted at BW. wangbin_pku@zju.edu.cn. The lead author (BW) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained. The datasets used and analyzed in this study are available upon reasonable request from the corresponding author.
Abbreviations
- OA:
-
Osteoarthritis
- MSCs:
-
Mesenchymal stem cells
- ncRNAs:
-
Non-coding RNAs
- circRNA:
-
Circular RNA
- lncRNA:
-
Long non-coding RNA
- miRNA:
-
MicroRNA
- mRNA:
-
Messenger RNA
- GO:
-
Gene Ontology
- KEGG:
-
Kyoto Encyclopedia of Genes and Genomes
- QUADAS-2:
-
Quality Assessment of Diagnostic Accuracy Studies-2
- HRs:
-
Hazard ratios
- Cis:
-
Confidence intervals
- logOR:
-
Log-odds-ratio
- BP:
-
Biological processes
- CC:
-
Cellular component
- MF:
-
Molecular function
- MSCs:
-
Mesenchymal stem cells
- TGF:
-
Transforming growth factor
- VEGF:
-
Vascular endothelial growth factor
- BMP:
-
Bone morphogenetic protein
- MMP:
-
Matrix metalloproteinase
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Funding
This study was supported by the National Natural Science Foundation of China (81802204) and by Zhejiang University School of Medicine, The First Affiliated Hospital’s Foundation (G2022010-18), Alibaba Cloud, Natural Science Foundation of Zhejiang Province (LTGY23H060007), and Zhejiang Medical and Health Science and Technology Project (2023RC010). The founders had no role in considering the study design or in the collection, analysis, interpretation of data, writing of the report, or decision to submit the article for publication.
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HCL, LY, and XKL contributed equally to this work. BW, HCL and LY conceived the idea for the review. BW, HCL, and LY designed, undertook the literature search, and coordinated the study. XKL, DJL, GSW, NNS, and JJL gave crucial intellectual input and provided critical revision for the initial protocol. XKL and DJL contributed to the implementation of the study. HCL, LY, and XKL acquired data, screened records, extracted data, and assessed risk of bias. HCL coded the statistical analysis, figures, and appendix in collaboration with LY and XKL. NNS, JJL, and BW analyzed and interpreted the data. HCL, LY, and BW wrote the first draft of the manuscript. All authors gave crucial feedback on the revised report and approved the final version of the manuscript. BW obtained funding. HCL, YL, XKL, and BW are the guarantors of this manuscript. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.
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Liu, H., Yan, L., Li, X. et al. MicroRNA expression in osteoarthritis: a meta-analysis. Clin Exp Med 23, 3737–3749 (2023). https://doi.org/10.1007/s10238-023-01063-8
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DOI: https://doi.org/10.1007/s10238-023-01063-8