Characterization of Neopeptides in Equine Articular Cartilage Degradation

被引:14
作者
Peffers, Mandy Jayne [1 ]
Thornton, David James [2 ]
Clegg, Peter David [1 ]
机构
[1] Univ Liverpool, Inst Ageing & Chron Dis, Dept Musculoskeletal Biol, Chester High Rd, Wirral CH64 7TE, Merseyside, England
[2] Wellcome Trust Ctr Cell Matrix Res, Fac Life Sci, Michael Smith Bldg,Oxford Rd, Manchester M13 9PT, Lancs, England
基金
英国惠康基金;
关键词
osteoarthritis; neopeptides; cartilage; equine; AGGRECANASE ACTIVITY; MASS-SPECTROMETRY; MATRIX METALLOPROTEINASES; OSTEOARTHRITIC CARTILAGE; RHEUMATOID-ARTHRITIS; KNEE OSTEOARTHRITIS; PROTEOMIC ANALYSIS; SYNOVIAL-FLUID; CLEAVAGE SITES; IDENTIFICATION;
D O I
10.1002/jor.22963
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
Osteoarthritis is characterized by a loss of extracellular matrix that leads to cartilage degradation and joint space narrowing. Specific proteases, including the aggrecanases ADAMTS-4 and matrix metalloproteinase 3, are important in initiating and promoting cartilage degradation in osteoarthritis. This study investigated protease-specific and disease-specific cleavage patterns of particular extracellular matrix proteins by comparing new peptide fragments, neopeptides, in specific exogenous protease-driven digestion of a crude cartilage proteoglycan extract and an in-vitro model of early osteoarthritis. Additionally, equine cartilage explants were treated with interleukin-1 and the media collected. Proteolytic cleavage products following trypsin digestion were then identified using tandem mass spectrometry. Complete sequences of proteolytically cleaved neopeptides were determined for the major cartilage proteoglycans aggrecan, biglycan, decorin, fibromodulin plus cartilage oligomeric matrix protein. The generation of neopeptides varied with enzyme specificity; however, some peptides were common to all samples. Previous known and novel cleavage sites were identifies. The identification of novel peptide fragments provides a platform for the development of antibodies that could assist in the identification of biomarkers for osteoarthritis (OA), as well as the identification of basic biochemical processes underlying OA. (C) 2015 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society.
引用
收藏
页码:106 / 120
页数:15
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