Proteomic analysis of articular cartilage vesicles from normal and osteoarthritic cartilage. Arthritis Rheum 2011 Feb;63(2):401-11
Date
02/01/2011Pubmed ID
21279997Pubmed Central ID
PMC3038242DOI
10.1002/art.30120Scopus ID
2-s2.0-79551658047 (requires institutional sign-in at Scopus site) 70 CitationsAbstract
OBJECTIVE: Articular cartilage vesicles (ACVs) are extracellular organelles found in normal articular cartilage. While they were initially defined by their ability to generate pathologic calcium crystals in cartilage of osteoarthritis (OA) patients, they can also alter the phenotype of normal chondrocytes through the transfer of RNA and protein. The purpose of this study was to analyze the proteome of ACVs from normal and OA human cartilage.
METHODS: ACVs were isolated from cartilage samples from 10 normal controls and 10 OA patients. We identified the ACV proteomes using in-gel trypsin digestion, nanospray liquid chromatography tandem mass spectrometry analysis of tryptic peptides, followed by searching an appropriate subset of the Uniprot database. We further differentiated between normal and OA ACVs by Holm-Sidak analysis for multiple comparison testing.
RESULTS: More than 1,700 proteins were identified in ACVs. Approximately 170 proteins satisfied our stringent criteria of having >1 representative peptide per protein present, and a false discovery rate of ≤5%. These proteins included extracellular matrix components, phospholipid binding proteins, enzymes, and cytoskeletal components, including actin. While few proteins were seen exclusively in normal or OA ACVs, immunoglobulins and complement components were present only in OA ACVs. Compared to normal ACVs, OA ACVs displayed decreases in matrix proteoglycans and increases in transforming growth factor β-induced protein βig-H3, DEL-1, vitronectin, and serine protease HtrA1 (P < 0.01).
CONCLUSION: These findings lend support to the concept of ACVs as physiologic structures in articular cartilage. Changes in OA ACVs are largely quantitative and reflect an altered matrix and the presence of inflammation, rather than revealing fundamental changes in composition.
Author List
Rosenthal AK, Gohr CM, Ninomiya J, Wakim BTAuthor
Ann K. Rosenthal MD Associate Dean, Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Cartilage, ArticularChondrocytes
Chromatography, High Pressure Liquid
Humans
Microchemistry
Nanotechnology
Osteoarthritis, Knee
Proteomics
Spectrometry, Mass, Electrospray Ionization
Tandem Mass Spectrometry
Transport Vesicles
