Serum protein signatures detect early radiographic osteoarthritis

被引:47
作者
Ling, S. M. [1 ]
Patel, D. D. [2 ]
Garnero, P. [3 ]
Zhan, M. [1 ]
Vaduganathan, M. [1 ]
Muller, D. [1 ]
Taub, D. [1 ]
Bathon, J. M. [4 ]
Hochberg, M. [5 ]
Abernethy, D. R. [1 ]
Metter, E. J. [1 ]
Ferrucci, L. [1 ]
机构
[1] NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA
[2] Univ N Carolina, Thurston Arthrit Res Ctr, Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA
[3] INSERM, Res Unit & Synarc 664, F-69008 Lyon, France
[4] Johns Hopkins Med Inst, Div Rheumatol, Baltimore, MD 21205 USA
[5] Univ Maryland, Sch Med, Div Clin Immunol & Rheumatol, Baltimore, MD 21201 USA
基金
美国国家卫生研究院;
关键词
Osteoarthritis; Proteins; Biomarkers; Inflammation; Aging; RHEUMATOID-ARTHRITIS; CARTILAGE; KNEE; EXPRESSION; MICROARRAYS; AGGRECAN; HIP;
D O I
10.1016/j.joca.2008.05.004
中图分类号
R826.8 [整形外科学]; R782.2 [口腔颌面部整形外科学]; R726.2 [小儿整形外科学]; R62 [整形外科学(修复外科学)];
学科分类号
摘要
Objective: To test the hypothesis that early knee and hand osteoarthritis (OA) development is characterized by detectable changes in serum proteins relevant to inflammation, cell growth, activation, and metabolism several years before OA becomes radiographically evident. Methods: Using microarray platforms that simultaneously test 169 proteins relevant to inflammation, cell growth, activation and metabolism, we conducted a case-control study nested within the Baltimore Longitudinal Study of Aging (BLSA). Subjects included 22 incident cases of OA and 66 age-, sex- and body mass index (BMI)-matched controls. Serum samples tested were obtained at the time of radiographic classification as either case or control, and up to 10 years earlier at a time when all participants were free of radiographic OA. Proteins with mean signal intensities fourfold higher than background were compared between cases and controls using multivariate techniques. Results: Sixteen proteins were different between OA cases compared to controls. Four of these proteins [matrix metalloproteinase (MMP)-7, interleukin (IL)-15, plasminogen activator inhibitor (PAI)-1 and soluble vascular adhesion protein (sVAP)-1] were already different in samples obtained 10 years before radiographic classification and remained different at the time of diagnosis. Six additional proteins were only associated with subsequent OA development and not with established OA. Conclusions: Changes in serum proteins implicated in matrix degradation, cell activation, inflammation and bone collagen degradation products accompany early OA development and can precede radiographic detection by several years. Published by Elsevier Ltd on behalf of Ostecarthritis Research Society International.
引用
收藏
页码:43 / 48
页数:6
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