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Lysosomal Molecules are Up-Regulated in the Articular Cartilage Explants Subjected to Oxidative Stress and in the Cartilage from an Osteoarthritis-Induced Rat Model

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Osteoarthritis (OA) is a multifactorial disease that affects millions of people around the world and it is the most common joint disease. The purpose of this study was to examine the kinetics of the expression of some lysosomal molecules and cellular process involved in the ethiopathogenesis of OA within two experimental models; also we reviewed recent patents on lysosomal proteins and discuss its possible value as early OA biomarkers. Ultrastructural analysis of chondrocytes from the articular cartilage explants, which were induced to oxidative stress with H2O2 showed changes as: cellular shrinkage, nuclear condensation and large amount of vesicles, suggesting a cell death process. To determine the participation of lysosomes in the cell death process, we studied the expression of the lysosomal biomarkers, Cathepsin D and LIMP II using an Immunohistofluorescence procedure. Both proteins were up-regulated in the time course of the stress induction. Furthermore, Cathepsin D and TUNEL labels were found in the same chondrocytes suggesting that lysosomes have an important role in the chondrocytes death. Afterwards, the kinetic expression of Cathepsin D during the kinetics of OA pathogenesis in a rat model showed an up-regulation since 5 to 45 days after induction. Therefore our results strongly suggest a main role of lysosomal pathway in the chondrocytes death since the beginning of the degenerative process. Recent patents on lysosomal proteins have been published in several pathologies, different to cartilage disorders, opening the possibility that lysosomal molecules within the cartilage and the synovial fluid could be also useful as biomarkers for OA beginning and progression.
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Keywords: Apoptosis; H2O2; LIMP II; articular cartilage; autophagy; cathepsin D; chondroptosis; osteoarthritis; oxidative stress

Document Type: Research Article

Publication date: January 1, 2013

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  • Recent Patents on Biomarkers publishes review and research articles, and guest edited thematic issues on important recent patents on biomarkers. The coverage includes novel biomarkers in basic, medical, environmental, and pharmaceutical research. A selection of important and recent patents on biomarkers is also included in the journal. The journal is essential reading for all researchers involved in biomarker research and discovery. The journal also covers recent research (where patents have been registered) in fast emerging patent biomarker applications; discovery and validation are covered for drug discovery, clinical development and molecular diagnostics.
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