[en] OBJECTIVE: This study was undertaken to identify new biomarkers of osteoarthritis (OA) by proteomics analysis and to develop specific immunoassays to detect and quantify them. METHODS: Proteomics analysis was performed in urine samples from 10 women (mean+/-SD age 76.0+/-5.0 years) undergoing knee replacement surgery due to severe OA and 5 healthy women (mean+/-SD age 25.6+/-2.6 years). Protein content was analyzed by 2-dimensional differential gel electrophoresis. Protein spots that exhibited an OA:control abundance ratio of >/=1.5 were identified by mass spectrometry. Specific enzyme-linked immunosorbent assays were developed and validated in serum obtained from 236 healthy subjects ages 20-64 years and from 76 patients with severe radiologic knee OA (mean+/-SD age 68.8+/-11.9 years). Immunohistochemical analysis was performed on articular cartilage from tibial plateaus. RESULTS: Thirteen proteins within spots that were significantly modified between groups were identified. Two peptides of fibulin 3, named Fib3-1 and Fib3-2, were of particular interest. Two antisera directed against these peptides were used to develop immunoassays. Compared with age-matched healthy subjects, median levels of serum Fib3-1 and Fib3-2 were elevated in OA patients (54.6 pM versus 85.1 pM [P<0.0001] and 144.4 pM versus 191.4 pM [P<0.0001], respectively). Using area under the receiver operating characteristic curve analysis, we demonstrated that Fib3-1 and Fib3-2 levels discriminate between OA and normal populations. Immunostaining revealed the presence of Fib3-1 and Fib3-2 in chondrocytes and in the extracellular matrix of the superficial layer of the fibrillated cartilage. CONCLUSION: Our findings indicate that Fib3-1 and Fib3-2 are potential biochemical markers for the diagnosis of OA.
Disciplines :
Rheumatology
Author, co-author :
Henrotin, Yves ; Université de Liège - ULiège > Département des sciences de la motricité > Unité de recherche sur l'os et le cartillage (U.R.O.C.)
Gharbi, Myriam
Mazzucchelli, Gabriel ; Université de Liège - ULiège > Center for Analytical Research and Technology (CART)
Dubuc, Jean-Emile
De Pauw, Edwin ; Université de Liège - ULiège > Département de chimie (sciences) > GIGA-R : Laboratoire de spectrométrie de masse (L.S.M.)
DEBERG, Michelle ; Centre Hospitalier Universitaire de Liège - CHU > Génétique
Language :
English
Title :
Fibulin 3 peptides Fib3-1 and Fib3-2 are potential biomarkers of osteoarthritis.
Publication date :
2012
Journal title :
Arthritis and Rheumatism
ISSN :
0004-3591
eISSN :
1529-0131
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Volume :
64
Issue :
7
Pages :
2260-7
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2012 by the American College of Rheumatology.
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