Fibulin 3 peptides Fib3‐1 and Fib3‐2 are potential biomarkers of osteoarthritis

Abstract

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 immuno- Osteoarthritis (OA) is a progressive disorder characterized by synovial inflammation, bone remodeling, and degradation of the extracellular matrix of articular cartilage (1,2). Currently, the diagnosis of OA is based on clinical and radiographic changes which occur late in disease progression. This method does not allow early detection of structural damage, and it is cumbersome to use in daily practice. Some of the available imaging methods lack reproducibility and sensitivity, and thus long-term followup of a large population is required to demonstrate the efficacy of a drug. This constitutes an impediment to new drug development. Therefore, there is an acute need for reliable biochemical markers that can facilitate the diagnosis of OA and inform prognosis, monitoring, and therapeutic strategies for the disease.Biochemical markers of bone, synovium, or cartilage turnover have been proposed as tools for the diagnosis and prognosis of OA and for the monitoring of OA treatment (3-5). The following 5 serum and urinary biomarkers are receiving increasing attention: serum hyaluronic acid (HA), serum cartilage oligomeric matrix protein (COMP), urinary C-telopeptide of type II colSupported by a grant from the government of the Walloon Region of Belgium.

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“…Excessive oxidative stress does not modify Fibulin-3 expression in VSMCs. However, oxidation may render Fibulin-3 biologically inactive [1, 2, 62-64]. Further studies are clearly required to elucidate whether Fibulin-3 function is affected by calcific conditions in VSMCs.…”

18F-FPRGD2 PET/CT imaging of musculoskeletal disorders

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