Signature of circulating microRNAs in osteoarthritis

Ann Rheum Dis. 2015 Mar;74(3):e18. doi: 10.1136/annrheumdis-2013-204698. Epub 2014 Feb 10.

Abstract

Background: Osteoarthritis is the most common form of arthritis and a major socioeconomic burden. Our study is the first to explore the association between serum microRNA levels and the development of severe osteoarthritis of the knee and hip joint in the general population.

Methods: We followed 816 Caucasian individuals from 1995 to 2010 and assessed joint arthroplasty as a definitive outcome of severe osteoarthritis of the knee and hip. After a microarray screen, we validated 12 microRNAs by real-time PCR in the entire cohort at baseline.

Results: In Cox regression analysis, three microRNAs were associated with severe knee and hip osteoarthritis. let-7e was a negative predictor for total joint arthroplasty with an adjusted HR of 0.75 (95% CI 0.58 to 0.96; p=0.021) when normalised to U6, and 0.76 (95% CI 0.6 to 0.97; p=0.026) after normalisation to the Ct average. miRNA-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI 0.61 to 0.97; p=0.028) when normalised to U6. This correlation was lost when data were normalised to Ct average (p=0.118). Finally, miRNA-885-5p showed a trend towards a positive relationship with arthroplasty when normalised to U6 (HR 1.24; 95% CI 0.95 to 1.62; p=0.107) or to Ct average (HR 1.30; 95% CI 0.99 to 1.70; p=0.056).

Conclusions: Our study is the first to identify differentially expressed circulating microRNAs in osteoarthritis patients necessitating arthroplasty in a large, population-based cohort. Among these microRNAs, let-7e emerged as potential predictor for severe knee or hip osteoarthritis.

Keywords: Knee Osteoarthritis; Orthopedic Surgery; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arthroplasty, Replacement, Hip
  • Arthroplasty, Replacement, Knee
  • Cohort Studies
  • Female
  • Humans
  • Longitudinal Studies
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Osteoarthritis, Hip / blood
  • Osteoarthritis, Hip / genetics*
  • Osteoarthritis, Hip / surgery
  • Osteoarthritis, Knee / blood
  • Osteoarthritis, Knee / genetics*
  • Osteoarthritis, Knee / surgery
  • Proportional Hazards Models
  • Prospective Studies
  • Real-Time Polymerase Chain Reaction
  • Severity of Illness Index

Substances

  • MIRN454 microRNA, human
  • MIRN885 microRNA, human
  • MicroRNAs
  • mirnlet7 microRNA, human