MicroRNA Signatures in Cartilage Ageing and Osteoarthritis

Panagiotis Balaskas, Katarzyna Goljanek-Whysall, Peter D. Clegg, Yongxiang Fang, Andy Cremers, Aibek Smagul, Tim J. M. Welting, Mandy J. Peffers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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-1 beta. Expression of these microRNAs decreased in human primary chondrocytes treated with IL-1 beta. 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.
Original languageEnglish
Article number1189
Number of pages27
JournalBiomedicines
Volume11
Issue number4
DOIs
Publication statusPublished - 1 Apr 2023

Keywords

  • osteoarthritis
  • knee cartilage
  • microarray
  • miR-107
  • miR-143-3p
  • CHONDROCYTE PROLIFERATION
  • KNEE OSTEOARTHRITIS
  • ARTICULAR-CARTILAGE
  • ENRICHMENT ANALYSIS
  • MATRIX DEGRADATION
  • DOWN-REGULATION
  • PATHOGENESIS
  • CONTRIBUTES
  • EXPRESSION
  • INFLAMMATION

Fingerprint

Dive into the research topics of 'MicroRNA Signatures in Cartilage Ageing and Osteoarthritis'. Together they form a unique fingerprint.

Cite this