Anabolic and catabolic gene expression pattern analysis in normal versus osteoarthritic cartilage using complementary DNA-array technology

Objective. To understand changes in gene expression levels that occur durin g osteoarthritic (OA) cartilage degeneration, using complementary DNA (cDNA )array technology. Methods. Nine normal, 6 early degenerated, and 6 late-stage OA cartilage sa mples of human knee joints were analyzed using the Human Cancer 1.2 cDNA ar ray and TaqMan analysis. Results. In addition to a large variability of expression levels between di fferent patients, significant expression patterns were detectable for many genes. Cartilage types II and VI collagen were strongly expressed in late-s tage specimens, reflecting the high matrix-remodeling activity of advanced OA cartilage. The increase in fibronectin expression in early degeneration suggests that fibronectin is a crucial regulator of matrix turnover activit y of chondrocytes during early disease development. Of the matrix metallopr oteinases (MMPs), MMP-3 appeared to be strongly expressed in normal and ear ly degenerative cartilage and downregulated in the late stages of disease. This indicates that other degradation pathways might be more important in l ate stages of cartilage degeneration, involving other enzymes, such as MMP- 2 and MMP-11, both of which were up-regulated in late-stage disease. MMP-11 was up-regulated in OA chondrocytes and, interestingly, also in the early- stage samples. Neither MMP-1 nor MMP-8 was detectable, and MMP-13 and MMP-2 were significantly detectable only in late-stage specimens, suggesting tha t early stages are characterized more by degradation of other matrix compon ents, such as aggrecan and other noncollagenous molecules, than by degradat ion of type II collagen fibers. Conclusion. This investigation allowed us to identify gene expression profi les of the disease process and to get new insights into disease mechanisms, for example, to develop a picture of matrix proteinases that are different ially involved in different phases of the disease process.