Current Drug Targets

Francis J. Castellino
Kleiderer-Pezold Professor of Biochemistry
Director, W.M. Keck Center for Transgene Research
Dean Emeritus, College of Science
230 Raclin-Carmichael Hall, University of Notre Dame
Notre Dame, IN 46556
USA

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Pathobiology of Osteoarthritis: Pathomechanisms and Potential Therapeutic Targets

Author(s): H. I. Roach, T. Aigner, S. Soder, J. Haag, H. Welkerling.

Abstract:

Osteoarthritis, a degenerative joint disease, is the most disabling condition of the Western world. It affects first and foremost the articular cartilages and leads to a molecular and supramolecular destruction of the extracellular cartilage matrix. In addition, the cells, the chondrocytes, show severe alterations of their phenotype: they get anabolically and catabolically activated, change accordingly their gene expression pattern, lose their differentiated phenotype, and undergo focally cell death and cell degeneration. All these processes represent potential targets for therapeutic intervention and drug development. Apart from the cartilage itself, however, other joint tissues are also involved in the disease: thus, the synovial capsule and membrane as well as the subchondral bone account not only for most of the symptoms of the disease, but are also presumably involved in the progression of the degenerative process. Both, inflammation and stiffening within the joint capsule accelerate joint destruction. Stiffening of the subchondral bone increases the mechanical stress over the overlying cartilage during physiological movement. Altogether, there is a plethora of tissues, disease processes and targets for treating osteoarthritic joint degeneration, which will need to be followed up systematically in the future.

Keywords: Apoptosis, osteoarthritis, cartilage, therapy, chondrocytes

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Article Details

VOLUME: 8
ISSUE: 2
Year: 2007
Page: [271 - 282]
Pages: 12
DOI: 10.2174/138945007779940160
Price: $58