Role of chondrocyte death and hypocellularity in ageing human articular cartilage and the pathogenesis of osteoarthritis

Abstract 

Apoptotic death of articular chondrocytes has been implicated in the pathogenesis of human osteoarthritis. Although nitric oxide and Fas ligand have been shown to be inducers of chondrocyte apoptosis in vitro and in vivo, the contribution of other triggers such as hypoxia, matrix acidosis, abnormal shear stress and catabolic cytokines like interleukin-1β and tumour necrosis factor α has not been examined. It is also not known if growth factors such as insulin like growth factor 1 or anabolic cytokines prevent apoptosis. The intracellular mechanism of effecting apoptotic death depend on whether damage to the mitochondrion or receptor ligation is the primary apoptotic stimulus, since these activate different initiator caspases which then deliver the apoptotic signal to common downstream effector caspases and other proteases. The hypothesis proposed here suggests that by using chondrocytes derived from control and osteoarthritis joints and established human chondrocyte cell lines, it is possible to investigate the relative contributions of major cell death inducing mechanisms and correspondingly which initiating caspase is activated. This understanding is essential for developing appropriately targeted anti-protease therapies for the inhibition of chondrocyte apoptosis in the rational treatment of osteoarthritis.

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• f1 Correspondence to: Dr. A. Mobasheri, Lecturer in Veterinary Biology, Department of Veterinary Preclinical Sciences, Faculty of Veterinary Science, The University of Liverpool, Brownlow Hill and Crown Street, Liverpool, L69 7ZJ, UK. Phone: +441517944284; Fax: +441517944243; E-mail:a.mobasheri@liverpool.ac.uk