Abstract
Objective. Information about the distribution of
proteins and the modulation that they undergo in the
different phases of rheumatic pathologies is essential
to understanding the development of these diseases. We
undertook this study to demonstrate the utility of mass
spectrometry (MS)–based molecular imaging for studying
the spatial distribution of different components in
human articular cartilage sections.
Methods. We compared the distribution of peptides
and proteins in human control and osteoarthritic
(OA) cartilage. Human control and OA cartilage slices
were cut and deposited on conductive slides. After
tryptic digestion, we performed matrix-assisted laser
desorption ionization–imaging MS (MALDI-IMS) experiments
in a MALDI–quadrupole time-of-flight mass
spectrometer. Protein identification was undertaken
with a combination of multivariate statistical methods
and Mascot protein database queries. Hematoxylin and
eosin staining and immunohistochemistry were performed
to validate the results.
Results. We created maps of peptide distributions
at 150- m raster size from control and OA human
cartilage. Proteins such as biglycan, prolargin, decorin,
and aggrecan core protein were identified and localized.
Specific protein markers for cartilage oligomeric matrix
protein and fibronectin were found exclusively in OA
cartilage samples. Their distribution displayed a stronger
intensity in the deep area than in the superficial
area. New tentative OA markers were found in the deep
area of the OA cartilage.
Conclusion. MALDI-IMS identifies and localizes
disease-specific peptides and proteins in cartilage. All
the OA-related peptides and proteins detected display a
stronger intensity in the deep cartilage. MS-based molecular
imaging is demonstrated to be an innovative
method for studying OA pathology.
Original language | English |
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Pages (from-to) | 710-720 |
Number of pages | 11 |
Journal | Arthritis and Rheumatism |
Volume | 65 |
Issue number | 3 |
DOIs | |
Publication status | Published - 2013 |