Pathology and Development - Developmental Systems for Target Validation and Drug Screening in Osteoarthritis

Author(s): N. Gerwin, T. Pellas, U. Junker, T. Aigner

Journal Name: Drug Design Reviews - Online (Discontinued)

Volume 2 , Issue 6 , 2005

Abstract:

Genomics projects elucidating the molecular mechanisms of osteoarthritis are complicated by the simultaneous appearance of many different and in part contrary pathways in diseased cartilage. To view a potential function of genes being differentially expressed in osteoarthritis, it has proven extremely useful to investigate their expression patterns in the developing skeleton. There, counteractive processes such as cartilage synthesis and degradation are separated in a spatio-temporal manner. Accordingly, expression analysis of osteoarthritis-relevant genes on developing skeletal tissues can provide early evidence for a potential pathway in which they may function. For pharmaceutical treatment of osteoarthritis, inhibition of cartilage degradation by inactivation of proteolytic enzymes, or stimulation of anabolic activities for cartilage restoration and neosynthesis are the two major logical approaches. For both aspects molecular concepts have been developed which are strongly supported by developmental studies. Gene targeting in mice has provided important information about the impact of individual matrix metalloproteinases (MMPs) in osteoarthritic cartilage degradation, as well as the essential role of Sox transcription factor family members in cartilage anabolism. On the basis of these studies, powerful developmental tools are available to study the in vivo efficacy of MMP inhibitors and to develop drugs to restore cartilage function in patients with osteoarthritis.

Keywords: cartilage, catabolism, anabolism, collagen, sox, matrix metalloproteinases

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Article Details

VOLUME: 2
ISSUE: 6
Year: 2005
Page: [435 - 448]
Pages: 14
DOI: 10.2174/1567269054867013
Price: $58

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