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Phenotypic modulation of chondrocytes as a potential therapeutic target in osteoarthritis: a hypothesis
  1. T Aignera,
  2. J Dudhiab
  1. aInstitute of Pathology, University of Erlangen-Nürnberg, Germany , bKennedy-Institute of Rheumatology, London
  1. Dr T Aigner, Institute of Pathology, University of Erlangen-Nürnberg, Krankenhausstr 8-10, D-91054 Erlangen, Germany.

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One central hallmark of osteoarthritic cartilage degeneration is the loss of matrix molecules, in particular proteoglycans. However, chondrocytes of osteoarthritic cartilage are generally thought to be anabolically hyperactive. Thus, in osteoarthritic cartilage degeneration, the ongoing net loss of the cartilage matrix components is attributed not to a lack of synthesis of cartilage matrix molecules by the cartilage cells, but to an increase in matrix catabolism by most authors.1-3 In contrast, our in situ analysis on the single cell level showed a suppression of aggrecan and collagen type II expression in the chondrocytes in the upper cartilage zone, which is critical for the progression of the cartilage destruction. Phenotyping of the osteoarthritic chondrocytes in this zone furthermore shows that the decrease in anabolic activity was presumably not simply because of cell deactivation, but may entail a specific cell differentiation pathway taken by the osteoarthritic chondrocytes. Based on our in situ analyses, we suggest a three step process of cellular events as one central pathway during osteoarthritic cartilage destruction. We conclude that stimulation of matrix anabolism via redifferentiation of osteoarthritic chondrocytes may be a relevant goal in future therapeutic approaches to osteoarthritic cartilage destruction.

Central observations

The functioning of articular cartilage is dependent on its extracellular matrix, which is synthesised and maintained by the cartilage cells, the chondrocytes. The functional properties of cartilage matrix are mainly provided by a network of type II collagen fibres4 and the entrapped aggregates of the proteoglycan aggrecan.5 The hallmarks of osteoarthritic cartilage degeneration are depletion of the matrix proteoglycans, damage to the collagen network, and finally, progressing matrix erosion.3 ,6-8 Based on our own work and that of others, we present a hypothesis for the basis of progressive cartilage destruction, focusing on the selective changes that occur in the different cartilage zones.

Generally, …

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