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Current Drug Targets
ISSN (Print): 1389-4501
ISSN (Online): 1873-5592
VOLUME: 8
ISSUE: 2
DOI: 10.2174/138945007779940025      Price:  $58









Cell Death and Apoptosis in Ostearthritic Cartilage

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Author(s): H. A. Kim and F. J. Blanco
Pages 333-345 (13)
Abstract:
Osteoarthritis (OA) is the most common chronic joint disease in the elderly population, causing significant pain and disability. Because the cardinal feature of OA is a progressive loss of articular cartilage, a great portion of the research endeavour into the pathogenesis of OA has been focused on the regulation of matrix synthesis and degradation. The phenotypic stability and survival of the chondrocytes are essential for the maintenance of a proper cartilage matrix. This has lead to the long-standing assumption that cell death is a central feature in OA cartilage degeneration. The important role of apoptosis in OA has been demonstrated in in vitro and in vivo models. However, it should be noted that the relative contribution of apoptotic cell death in the pathogenesis of OA is still difficult to assess because of the chronic nature of the disease process. Therefore, the apoptosis of chondrocytes seems to be a potential target for therapeutic interventions in OA. The death receptor, mitochondrial and endoplasmic reticulum pathways are the major cellular pathways of apoptosis. Of all these elements involved in the apoptosis of chondrocytes, caspase inhibition has been studied with the most detail. Other molecules with the capacity to modulate mitochondria function, phosphatase (PP-1A/B) activity and pro-apoptosis stimuli (NO, prostaglandins, cytokines, ROS) could be excellent targets to block apoptosis of chondrocytes. Finally, the regulation of the natural inhibitors of apoptosis (c-FLIP, BAR, ARC and HC-gp39) could complement the other strategies to reduce cartilage degradation.
Keywords:
Osteoarthritis, caspases, chondrocytes, apoptosis, nitric oxide, chondroptosis, Fas-ligand, mitochondria
Affiliation:
Osteoarticular and Aging Research Lab. Biomedical Research Center, CH Universitario Juan Canalejo,A Coruna, Spain.