Gene expression profiling of serum- and interleukin-1 beta-stimulated primary human adult articular chondrocytes--a molecular analysis based on chondrocytes isolated from one donor.
In order to understand the cellular disease mechanisms of osteoarthritic cartilage degeneration it is of primary importance to understand both the anabolic and the catabolic processes going on in parallel in the diseased tissue. In this study, we have applied cDNA-array technology (Clontech) to study gene expression patterns of primary human normal adult articular chondrocytes isolated from one donor cultured under anabolic (serum) and catabolic (IL-1beta) conditions. Significant differences between the different in vitro cultures tested were detected. Overall, serum and IL-1beta significantly altered gene expression levels of 102 and 79 genes, respectively. IL-1beta stimulated the matrix metalloproteinases-1, -3, and -13 as well as members of its intracellular signaling cascade, whereas serum increased the expression of many cartilage matrix genes. Comparative gene expression analysis with previously published in vivo data (normal and osteoarthritic cartilage) showed significant differences of all in vitro stimulations compared to the changes detected in osteoarthritic cartilage in vivo. This investigation allowed us to characterize gene expression profiles of two classical anabolic and catabolic stimuli of human adult articular chondrocytes in vitro. No in vitro model appeared to be adequate to study overall gene expression alterations in osteoarthritic cartilage. Serum stimulated in vitro cultures largely reflected the results that were only consistent with the anabolic activation seen in osteoarthritic chondrocytes. In contrast, IL-1beta did not appear to be a good model for mimicking catabolic gene alterations in degenerating chondrocytes.
Aigner
Thomas
T
Osteoarticular and Arthritis Research, Department of Pathology, University of Erlangen-Nürnberg, Krankenhausstr 8-10, D-91054 Erlangen, FRG. thomas.aigner@patho.imed.uni-erlangen.de
McKenna
Louise
L
Zien
Alexander
A
Fan
Zhiyong
Z
Gebhard
Pia M
PM
Zimmer
Ralf
R
D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000166:cytology / Q000378:metabolism*; D002469:Cell Separation / Q000379:methods; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020869:Gene Expression Profiling; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D044967:Serum / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D016207:Cytokines; D006133:Growth Substances; D007375:Interleukin-1; D020782:Matrix Metalloproteinases