The causes of osteoarthritis are diverse, notes Dr. Yefu Li of the Harvard School of Dental Medicine. Mutations in two types of collagens, type IX and XI, have been linked to early-onset osteoarthritis but the link between the collagen mutations and the pathogenesis of osteoarthritis is not yet clear.
To further elucidate the relationship between collagen mutations and the pathogenesis of osteoarthritis, Dr. Yefu Li and colleagues studied mice with a mutation in type XI collagen. These mice exhibit age-related osteoarthritis.
Dr. Li and his colleagues found that the mutant mice had increased amounts of the protein discoidin domain receptor 2 (DDR2) in the articular cartilage chondrocytes of their knee joints. "DDR2 is a signalling receptor on cell surfaces that binds to collagen fibrils outside the cells," explains Dr. Li. "The normal function of DDR2 is largely unknown. One report demonstrates that the lack of DDR2 results in dwarfism in mice, probably due to decreased proliferation of cartilage cells during bone growth."
The increase in DDR2 caused an increase in the expression of matrix metalloproteinase-13 (MMP-13), a protein that remodels the extracellular matrix by degrading major matrix components.
"Our study suggests that collagen binds to DDR2 and stimulates the production of MMP-13, that in turn degrades the cartilage," concludes Dr. Li. "Our study also identifies a signalling pathway in cartilage cells used by DDR2 to regulate the synthesis of MMP-13. Our results bring us one step closer to identifying a possible early and common step in the development of different forms of osteoarthritis."
Dr. Li's results suggest that inhibitors of DDR2 signalling may be useful as drugs to slow down osteoarthritis progression.
MEDICA.de; Source: American Society for Biochemistry and Molecular Biology