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Expression of syndecan-1 during development, growth and cartilage degeneration in a transgenic mouse model for osteoarthritis

Mice heterozygous for the Del1 transgene locus with short deletion mutation in typeII collagen gene develop degenerative changes in the knee joints from the age of 3 months which progresses to an end-stage OA by the age of 12–15 months. This study focuses on expression and distribution in syndecan-1 during development of osteoarthritic cartilage degeneration. Human samples from cartilage of osteoarthritic patients was studied for comparison. Northern analysis of total RNA extracted from knee joints of transgenic Del1 mice and their nontransgenic controls was used to monitor changes in syndecan-1 levels during development, growth, aging and cartilage degeneration. Immunohistochemistry was used to study the distribution of syndecan-1 in mouse and human samples. Syndecan-1 was present in the knee joints during development, growth and aging both in the control and Del1 mice, the mRNA levels being highest in the aged and late osteoarthritic samples. The most intensive immunostaining of syndecan-1 was seen in synovial tissue and adjacent of the defected areas of cartilage and menisci. In addition, some individual cells or cell clusters in the superficial zone of articular cartilage contained syndecan-1. In human osteoarthritic cartilage, dedifferentiated syndecan-1 positive cells were seen in corresponding locations to those in Del1 mice. We demonstrated syndecan-1 for the first time in aging and degenerating murine articular cartilage and synovial tissue. Syndecan-1 is involved in phenotypic modulation of the articular chondrocytes and during osteophyte formation. In this Del1 mouse model, proliferation plays a role forming characteristic chondrocyte clusters near the surface, while apoptosis occurs primarily in the calcified cartilage. These results suggest that syndecan-1 has a role in the functional activity of the chondrocytes during the disease process. Control of syndecan expression in articular cartilage could be an attractive target for therapeutic interventions in the future.

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Pirilä, L., Salminen, H., Säämänen, A. et al. Expression of syndecan-1 during development, growth and cartilage degeneration in a transgenic mouse model for osteoarthritis. Arthritis Res Ther 4 (Suppl 1), 9 (2002).

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