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MicroRNA Signatures in Cartilage Ageing and Osteoarthritis
- Source :
- Biomedicines; Volume 11; Issue 4; Pages: 1189
- Publication Year :
- 2023
- Publisher :
- MDPI AG, 2023.
-
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 WNT4 and IHH, 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.
- Subjects :
- EXPRESSION
DOWN-REGULATION
knee cartilage
miR-107
PATHOGENESIS
miR-143-3p
Medicine (miscellaneous)
osteoarthritis
microarray
ARTICULAR-CARTILAGE
KNEE OSTEOARTHRITIS
CHONDROCYTE PROLIFERATION
General Biochemistry, Genetics and Molecular Biology
MATRIX DEGRADATION
CONTRIBUTES
INFLAMMATION
ENRICHMENT ANALYSIS
Subjects
Details
- Language :
- English
- ISSN :
- 22279059
- Volume :
- 11
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Biomedicines
- Accession number :
- edsair.doi.dedup.....54baa47dd5f9b904826a50f8ef781fc5
- Full Text :
- https://doi.org/10.3390/biomedicines11041189