2 research outputs found
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
Analysis of Autoantibody Profiles in Osteoarthritis Using Comprehensive Protein Array Concepts
Osteoarthritis
(OA) is the most common rheumatic disease and one
of the most disabling pathologies worldwide. To date, the diagnostic
methods of OA are very limited, and there are no available medications
capable of halting its characteristic cartilage degeneration. Therefore,
there is a significant interest in new biomarkers useful for the early
diagnosis, prognosis, and therapeutic monitoring. In the recent years,
protein microarrays have emerged as a powerful proteomic tool to search
for new biomarkers. In this study, we have used two concepts for generating
protein arrays, antigen microarrays, and NAPPA (nucleic acid programmable
protein arrays), to characterize differential autoantibody profiles
in a set of 62 samples from OA, rheumatoid arthritis (RA), and healthy
controls. An untargeted screen was performed on 3840 protein fragments
spotted on planar antigen arrays, and 373 antigens were selected for
validation on bead-based arrays. In the NAPPA approach, a targeted
screening was performed on 80 preselected proteins. The autoantibody
targeting CHST14 was validated by ELISA in the same set of patients.
Altogether, nine and seven disease related autoantibody target candidates
were identified, and this work demonstrates a combination of these
two array concepts for biomarker discovery and their usefulness for
characterizing disease-specific autoantibody profiles