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Activation of the Discoidin Domain Receptor 2 Induces Expression of Matrix Metalloproteinase 13 Associated with Osteoarthritis in Mice.
- Source :
-
Journal of Biological Chemistry . 1/7/2005, Vol. 280 Issue 1, p548-555. 8p. 3 Color Photographs, 2 Black and White Photographs, 1 Diagram, 13 Graphs. - Publication Year :
- 2005
-
Abstract
- Human genetic studies indicate that mutations in type IX and XI collagens result in early-onset osteoarthritis (OA) with a wide spectrum of osteochondrodysplasia. However, a convincing causal chain of events underlying the role of these collagen mutations in the pathogenesis of OA has not been elucidated. Here we show that the expression of a cell surface collagen receptor, discoidin domain receptor 2 (DDR2), is increased in chondrocytes of the articular cartilage of knee joints in mice that develop OA as a result of a heterozygous mutation in type XI collagen. At the same time point, 6 months, we also found increased expression and activity of matrix metalloproteinase 13 (MMP-13) in the mutant mouse knee cartilage. The expression of both DDR2 and MMP-13 was increased in chondrocytes cultured on plates coated with native type II collagen but not on gelatin, and overexpression of DDR2, but not of a truncated form, was found to induce the expression of MMP-13 when chondrocytes were cultured on type II collagen but not on plastic. The DDR2-induced expression of MMP-13 appears to be specific, since we did not observe induction of MMP-1, MMP-3, MMP-8, ADAMTS-4, ADAMTS-5, and IL-1 transcripts in human chondrocytes or Mmp-3, Mmp-8, Adamts-4, Adamts-5, and Il-1 in mouse chondrocytes. Our data suggest that the defect in the cartilage matrix of mice that are heterozygous for a type XI collagen mutation (cho/+) permits activation and upregulation of DDR2 in chondrocytes. This could be due to increased exposure of chondrocytes to type II collagen as a result of the decreased amount of type XI collagen in the mutant cartilage. The specific induction of MMP-13 by DDR2 in response to its cartilage-specific ligand, type II collagen, may contribute to cartilage damage in hereditary OA. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 280
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 15948797
- Full Text :
- https://doi.org/10.1074/jbc.M411036200