Quantitative proteomic profiling of human articular cartilage degradation in osteoarthritis.
Osteoarthritis (OA) is the most common rheumatic pathology and is characterized primarily by articular cartilage degradation. Despite its high prevalence, there is no effective therapy to slow disease progression or regenerate the damaged tissue. Therefore, new diagnostic and monitoring tests for OA are urgently needed, which would also promote the development of alternative therapeutic strategies. In the present study, we have performed an iTRAQ-based quantitative proteomic analysis of secretomes from healthy human articular cartilage explants, comparing their protein profile to those from unwounded (early disease) and wounded (advanced disease) zones of osteoarthritic tissue. This strategy allowed us to identify a panel of 76 proteins that are distinctively released by the diseased tissue. Clustering analysis allowed the classification of proteins according to their different profile of release from cartilage. Among these proteins, the altered release of osteoprotegerin (decreased in OA) and periostin (increased in OA), both involved in bone remodelling processes, was verified in further analyses. Moreover, periostin was also increased in the synovial fluid of OA patients. Altogether, the present work provides a novel insight into the mechanisms of human cartilage degradation and a number of new cartilage-characteristic proteins with possible biomarker value for early diagnosis and prognosis of OA.
Proteomics Group-PBR2-ProteoRed/ISCIII, Rheumatology Division, §RIER-RED de Inflamación y Enfermedades Reumáticas, ∥CIBER-BBN Instituto de Salud Carlos III, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Sergas, Universidade da Coruña (UDC) , As Xubias, 84, 15006-A Coruña, Spain.
Lucía
L
Lourido
Valentina
V
Calamia
Jesús
J
Mateos
Patricia
P
Fernández-Puente
Juan
J
Fernández-Tajes
Francisco J
FJ
Blanco
Cristina
C
Ruiz-Romero
D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D002853:Chromatography, Liquid; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010003:Osteoarthritis / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013582:Synovial Fluid / Q000378:metabolism; D053719:Tandem Mass Spectrometry; D046509:Tissue Culture Techniques
D015415:Biomarkers; D015815:Cell Adhesion Molecules; D053244:Osteoprotegerin; C512835:POSTN protein, human; D020543:Proteome
biomarkers; cartilage; osteoarthritis; proteomics; secretome