Quantitative proteomics reveals regulatory differences in the chondrocyte secretome from human medial and lateral femoral condyles in osteoarthritic patients

被引:31
作者
Stenberg, Johan [1 ]
Ruetschi, Ulla [1 ]
Skioldebrand, Eva [2 ]
Karrholm, Johan [3 ]
Lindahl, Anders [1 ,4 ]
机构
[1] Univ Gothenburg, Dept Clin Chem & Transfus Med, Inst Biomed, Sahlgrenska Acad,Sahlgrenska Univ Hosp, Gothenburg, Sweden
[2] Dept Biomed Sci & Vet Publ Hlth, Div Pathol Pharmacol & Toxicol, S-75007 Uppsala, Sweden
[3] Univ Gothenburg, Dept Orthopaed Surg, Inst Clin Sci, Sahlgrenska Acad, Gothenburg, Sweden
[4] Sahlgrens Univ Hosp, SE-41345 Gothenburg, Sweden
关键词
Secretome; SILAC; Chondrocyte; Osteoarthritis; Proteomics; ENDOTHELIAL-CELL MIGRATION; ARTICULAR-CARTILAGE; KNEE OSTEOARTHRITIS; BIOCHEMICAL MARKER; SIGNALING PATHWAY; PROTEIN; WNT; IDENTIFICATION; INHIBITION; ARTHRITIS;
D O I
10.1186/1477-5956-11-43
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Background: Osteoarthritis (OA) is a destructive joint disease and there are no known biomarkers available for an early diagnosis. To identify potential disease biomarkers and gain further insight into the disease mechanisms of OA we applied quantitative proteomics with SILAC technology on the secretomes from chondrocytes of OA knees, designated as high Mankin (HM) scored secretome. A quantitative comparison was made between the secretomes of the medial and lateral femur condyle chondrocytes in the same knee since the medial femur condyle is usually more affected in OA than the lateral condyle, which was confirmed by Mankin scoring. The medial/lateral comparison was also made on the secretomes from chondrocytes taken from one individual with no clinically apparent joint-disease, designated as low Mankin (LM) scored secretome. Results: We identified 825 proteins in the HM secretome and 69 of these showed differential expression when comparing the medial and lateral femoral compartment. The LM scored femoral condyle showed early signs of OA in the medial compartment as assessed by Mankin score. We here report the identification and relative quantification of several proteins of interest for the OA disease mechanism e.g. CYTL1, DMD and STAB1 together with putative early disease markers e.g. TIMP1, PPP2CA and B2M. Conclusions: The present study reveals differences in protein abundance between medial/lateral femur condyles in OA patients. These regulatory differences expand the knowledge regarding OA disease markers and mechanisms.
引用
收藏
页数:15
相关论文
共 68 条
[1]   Developments in the scientific understanding of osteoarthritis [J].
Abramson, Steven B. ;
Attur, Mukundan .
ARTHRITIS RESEARCH & THERAPY, 2009, 11 (03)
[2]   THE PLACE OF HUMAN GAMMA-TRACE (CYSTATIN-C) AMONGST THE CYSTEINE PROTEINASE-INHIBITORS [J].
BARRETT, AJ ;
DAVIES, ME ;
GRUBB, A .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1984, 120 (02) :631-636
[3]  
Blom AB, 2010, CURR DRUG TARGETS, V11, P620
[4]  
Bonin-Debs AL, 2004, EXPERT OPIN BIOL TH, V4, P551, DOI 10.1517/eobt.4.4.551.29462
[5]   TREATMENT OF DEEP CARTILAGE DEFECTS IN THE KNEE WITH AUTOLOGOUS CHONDROCYTE TRANSPLANTATION [J].
BRITTBERG, M ;
LINDAHL, A ;
NILSSON, A ;
OHLSSON, C ;
ISAKSSON, O ;
PETERSON, L .
NEW ENGLAND JOURNAL OF MEDICINE, 1994, 331 (14) :889-895
[6]   Pharmacoproteomic Study of Three Different Chondroitin Sulfate Compounds on Intracellular and Extracellular Human Chondrocyte Proteomes [J].
Calamia, Valentina ;
Fernandez-Puente, Patricia ;
Mateos, Jesus ;
Lourido, Lucia ;
Rocha, Beatriz ;
Montell, Eulalia ;
Verges, Josep ;
Ruiz-Romero, Cristina ;
Blanco, Francisco J. .
MOLECULAR & CELLULAR PROTEOMICS, 2012, 11 (06)
[7]   Metabolic Labeling of Chondrocytes for the Quantitative Analysis of the Interleukin-1-beta-mediated Modulation of Their Intracellular and Extracellular Proteomes [J].
Calamia, Valentina ;
Rocha, Beatriz ;
Mateos, Jesus ;
Fernandez-Puente, Patricia ;
Ruiz-Romero, Cristina ;
Blanco, Francisco J. .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (08) :3701-3711
[8]   Transferrin promotes endothelial cell migration and invasion: Implication in cartilage neovascularization [J].
Carlevaro, MF ;
Albini, A ;
Ribatti, D ;
Gentili, C ;
Benelli, R ;
Cermelli, S ;
Cancedda, R ;
Cancedda, FD .
JOURNAL OF CELL BIOLOGY, 1997, 136 (06) :1375-1384
[9]   Wnt-β-catenin signaling in the pathogenesis of osteoarthritis [J].
Corr, Maripat .
NATURE CLINICAL PRACTICE RHEUMATOLOGY, 2008, 4 (10) :550-556
[10]   Andromeda: A Peptide Search Engine Integrated into the MaxQuant Environment [J].
Cox, Juergen ;
Neuhauser, Nadin ;
Michalski, Annette ;
Scheltema, Richard A. ;
Olsen, Jesper V. ;
Mann, Matthias .
JOURNAL OF PROTEOME RESEARCH, 2011, 10 (04) :1794-1805