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The Journal of Bone and Joint Surgery (American) 85:117-123 (2003)
© 2003 The Journal of Bone and Joint Surgery, Inc.

Scientific Article

Gene Expression in Chondrocytes Assessed with Use of Microarrays

Thomas Aigner, MD, Alexander Zien, PhD, Daniel Hanisch, MSc,, SCAI and Ralf Zimmer, PhD

Corresponding author: Thomas Aigner, MD
Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr. 8-10, D-91054 Erlangen, Germany. E-mail address: thomas.aigner{at}patho.imed.uni-erlangen.de

In support of their research or preparation of this manuscript, one or more of the authors received grants or outside funding from the German Ministry of Research (grants IZKF-D4 and 01GG9824). None of the authors received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the authors are affiliated or associated.

Background: Despite considerable limitations such as low sensitivity and insensitivity to alternative splicing, posttranscriptional regulation, and posttranslational modification, cDNA array technology provides a powerful tool with which to obtain an overview of gene expression patterns, hardly achievable with other techniques. This has been shown to be true for the analysis of known genes as well as the discovery of new genes of interest.

Methods: Samples of normal and late-stage osteoarthritic cartilage of human knee joints were analyzed with use of the Human Cancer 1.2 cDNA-array and TaqMan analysis.

Results: In spite of a large variability of expression levels among different patients, significant expression patterns for many known genes of interest such as cartilage matrix proteins (e.g., collagen types II, VI, and XI; aggrecan; decorin; biglycan) and matrix-degrading proteases were detected. Of the latter, MMP-3 appeared to be strongly expressed in normal and early degenerative cartilage and downregulated in the late disease stages. This indicates that, in the late stages of cartilage degeneration, other degradation pathways might be more important, for example, those involving enzymes such as MMP-2 and MMP-13, both of which were upregulated in late-stage disease.

Conclusion: Most results have to be considered to be preliminary to a certain degree, as technical tools and interpretation approaches are still emerging and need more validation. Clearly, there is a major challenge to distill information and knowledge out of the obtained mass of data. However, these data will be one basis of a new world of biological understanding. These new insights will be network-based and no longer molecule-centered. Today, molecules have a biochemical and physiological context; tomorrow, biological networks will have molecules as constituents.


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