Balaskas, Panagiotis, Goljanek-Whysall, Katarzyna 
ORCID: 0000-0001-8166-8800, Clegg, Peter D, Fang, Yongxiang, Cremers, Andy, Smagul, Aibek, Welting, Tim JM and Peffers, Mandy J ORCID: 0000-0001-6979-0440
(2023)
MicroRNA Signatures in Cartilage Ageing and Osteoarthritis.
BIOMEDICINES, 11 (4).
1189-.
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Abstract
Osteoarthritis is the most common degenerative joint disorder. MicroRNAs are gene expression regulators that act post-transcriptionally to control tissue homeostasis. Microarray analysis was undertaken in osteoarthritic intact, lesioned and young intact cartilage. Principal component analysis showed that young intact cartilage samples were clustered together; osteoarthritic samples had a wider distribution; and osteoarthritic intact samples were separated into two subgroups, osteoarthritic-Intact-1 and osteoarthritic-Intact-2. We identified 318 differentially expressed microRNAs between young intact and osteoarthritic lesioned cartilage, 477 between young intact and osteoarthritic-Intact-1 cartilage and 332 between young intact and osteoarthritic-Intact-2 cartilage samples. For a selected list of differentially expressed microRNAs, results were verified in additional cartilage samples using qPCR. Of the validated DE microRNAs, four-miR-107, miR-143-3p, miR-361-5p and miR-379-5p-were selected for further experiments in human primary chondrocytes treated with IL-1β. Expression of these microRNAs decreased in human primary chondrocytes treated with IL-1β. For miR-107 and miR-143-3p, gain- and loss-of-function approaches were undertaken and associated target genes and molecular pathways were investigated using qPCR and mass spectrometry proteomics. Analyses showed that <i>WNT4</i> and <i>IHH</i>, predicted targets of miR-107, had increased expression in osteoarthritic cartilage compared to young intact cartilage and in primary chondrocytes treated with miR-107 inhibitor, and decreased expression in primary chondrocytes treated with miR-107 mimic, suggesting a role of miR-107 in chondrocyte survival and proliferation. In addition, we identified an association between miR-143-3p and EIF2 signalling and cell survival. Our work supports the role of miR-107 and miR-143-3p in important chondrocyte mechanisms regulating proliferation, hypertrophy and protein translation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | osteoarthritis, knee cartilage, microarray, miR-107, miR-143-3p |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 05 Jun 2023 13:33 |
| Last Modified: | 05 Jun 2023 13:33 |
| DOI: | 10.3390/biomedicines11041189 |
| Open Access URL: | https://doi.org/10.3390%2Fbiomedicines11041189 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3170832 |
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