title: Signature of circulating microRNAs in osteoarthritis.
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.
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Christian
authors: C
authors: Beyer
authors: King's British Heart Foundation Centre, King's College London, London, UK.
authors: Anna
authors: A
authors: Zampetaki
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Neng-Yu
authors: NY
authors: Lin
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Arnd
authors: A
authors: Kleyer
authors: Rheumatology, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors: Carlo
authors: C
authors: Perricone
authors: Rheumatology, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy.
authors: Annamaria
authors: A
authors: Iagnocco
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Alfiya
authors: A
authors: Distler
authors: King's British Heart Foundation Centre, King's College London, London, UK.
authors: Sarah R
authors: SR
authors: Langley
authors: Department of Trauma Surgery, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Kolja
authors: K
authors: Gelse
authors: Department of Orthopedic Surgery, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Stefan
authors: S
authors: Sesselmann
authors: Departments of Radiology and Internal and Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
authors: Rolando
authors: R
authors: Lorenzini
authors: Department of Orthopaedics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Andreas
authors: A
authors: Niemeier
authors: Department of Orthopedic Surgery, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Bernd
authors: B
authors: Swoboda
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Jörg H W
authors: JH
authors: Distler
authors: Departments of Radiology and Internal and Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
authors: Peter
authors: P
authors: Santer
authors: Departments of Radiology and Internal and Laboratory Medicine, Bruneck Hospital, Bruneck, Italy.
authors: Georg
authors: G
authors: Egger
authors: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Johann
authors: J
authors: Willeit
authors: King's British Heart Foundation Centre, King's College London, London, UK.
authors: Manuel
authors: M
authors: Mayr
authors: Department of Internal Medicine 3 and Institute of Clinical Immunology, University Erlangen-Nuremberg, Erlangen, Germany.
authors: Georg
authors: G
authors: Schett
authors: Department of Neurology, Medical University of Innsbruck, Innsbruck, Austria.
authors: Stefan
authors: S
authors: Kiechl
mesh_terms: D000368:Aged; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D015207:Osteoarthritis, Hip / Q000097:blood / Q000235:genetics* / Q000601:surgery; D020370:Osteoarthritis, Knee / Q000097:blood / Q000235:genetics* / Q000601:surgery; D016016:Proportional Hazards Models; D011446:Prospective Studies; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index
chemical_list: C583712:MIRN454 microRNA, human; C574934:MIRN885 microRNA, human; D035683:MicroRNAs; C487931:mirnlet7 microRNA, human
keywords: Knee Osteoarthritis; Orthopedic Surgery; Osteoarthritis