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Extended report
Signature of circulating microRNAs in osteoarthritis
  1. Christian Beyer1,
  2. Anna Zampetaki2,
  3. Neng-Yu Lin1,
  4. Arnd Kleyer1,
  5. Carlo Perricone3,
  6. Annamaria Iagnocco3,
  7. Alfiya Distler1,
  8. Sarah R Langley2,
  9. Kolja Gelse4,
  10. Stefan Sesselmann5,
  11. Rolando Lorenzini6,
  12. Andreas Niemeier7,
  13. Bernd Swoboda5,
  14. Jörg H W Distler1,
  15. Peter Santer6,
  16. Georg Egger6,
  17. Johann Willeit8,
  18. Manuel Mayr2,
  19. Georg Schett1,
  20. Stefan Kiechl8
  1. 1Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany
  2. 2King's British Heart Foundation Centre, King's College London, London, UK
  3. 3Rheumatology, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
  4. 4Department of Trauma Surgery, University Erlangen-Nuremberg, Erlangen, Germany
  5. 5Department of Orthopedic Surgery, University Erlangen-Nuremberg, Erlangen, Germany
  6. 6Departments of Radiology and Internal and Laboratory Medicine, Bruneck Hospital, Bruneck, Italy
  7. 7Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany
  8. 8Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria
  1. Correspondence to Dr Christian Beyer, Department of Internal Medicine 3 and Institute of Clinical Immunology, Friedrich-Alexander-University Erlangen-Nuremberg, Ulmenweg 18, Erlangen 91054, Germany; christian.beyer{at}uk-erlangen.de

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.

  • Knee Osteoarthritis
  • Osteoarthritis
  • Orthopedic Surgery

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