  A significant association between a polymorphism in the D repeat of the gene
encoding asporin and osteoarthritis, the most frequent of articular diseases,
has been recently reported. The goal of the present study was to investigate
the expression of this new class I small leucine-rich proteoglycan (SLRP) in
human articular chondrocytes. First, we studied the modulation of asporin
(ASPN) expression by cytokines by Western blot and reverse
transcription-polymerase chain reaction. Interleukin-1$\beta$ and tumor
necrosis factor-$\alpha$ downregulated ASPN, whereas transforming growth
factor-$\beta$1 (when incubated in a serum-free medium) upregulated it.
Similarly to proinflammatory cytokines, chondrocyte dedifferentiation induced
by a successive passages of cells was accompanied by a decreased asporin
expression, whereas their redifferentiation by three-dimensional culture
restored its expression. Finally, we found an important role of the
transcription factor Sp1 in the regulation of ASPN expression. Sp1 ectopic
expression increased ASPN mRNA level and promoter activity. In addition, using
gene reporter assay and electrophoretic mobility shift assay, we showed that
Sp1 mediated its effect through a region located between -473 and -140 bp
upstream of the transcription start site in ASPN gene. In conclusion, this
report is the first study on the regulation of asporin expression by different
cytokines in human articular chondrocytes. Our data indicate that the
expression of this gene is finely regulated in cartilage and suggest a major
role of Sp1.
