Matrix assisted laser desorption ionization imaging mass spectrometry: a new methodology to study human osteoarthritic cartilage
The distribution of proteins and the modulation that they undergo in the different phases of rheumatic pathologies is essential to understand the development of these diseases. In this article we demonstrate the utility of MS based molecular imaging to study the spatial distribution of different components in human articular cartilage sections. Methods: We have 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, MALDI-IMS experiments were performed in a MALDI-Q-TOF mass spectrometer. Protein identification was undertaken with a combination of multivariate statistical methods and Mascot protein database queries. Hematoxylin-eosin staining and immunohistochemistry were performed to validate the results. Results: We have created maps of peptide distributions at 150 μm pixel size from control and OA human cartilage. Proteins such as biglycan (PGS1), prolargin (PRELP), decorin (PGS2) and aggrecan core protein (PGCA) were identified and localized. Specific protein markers for cartilage oligomeric matrix protein (COMP) and fibronectin (FINC) were exclusively found in the OA samples. Their distribution displayed a stronger intensity in the deep compared to the superficial area. New tentative OA markers were found in the deep area of the OA cartilage. Conclusions: 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. Mass spectrometry based molecular imaging is demonstrated to be an innovative method to study OA pathology.
Cillero Pastor, B, Eijkel, G.B, Kiss, A, Blanco Garcia, F.J, & Heeren, R.M.A. (2013). Matrix assisted laser desorption ionization imaging mass spectrometry: a new methodology to study human osteoarthritic cartilage. Arthr. Rheumat., 65(3), 710–720. doi:10.1002/art.37799