Antisense inhibition of CD44 tailless splice variant in human articular chondrocytes promotes hyaluronan internalization

Objective. To determine whether alternatively spliced variants of CD44, in particular a short, intracellular tail CD44 isoform, are used by articular chondrocytes to modulate the functions of this matrix receptor. Methods. Normal human articular chondrocytes were cultured with or without interleukin-1 alpha (IL-1 alpha), and the relative expression of CD44 exon 19 and CD44 exon 20, hyaluronan synthase 2, aggrecan, and GAPDH messenger R NA (mRNA) was determined using reverse transcriptase-polymerase chain react ion. Next, CD44 exon 19 mRNA was selectively inhibited by the use of antise nse oligonucleotides. The effects of exon 19 loss were analyzed by matrix a ssembly and hyaluronan internalization assays. Results. Human articular chondrocytes express varying levels of exon 19 (sh ort tail)- and exon 20 (long tail)-containing CD44 mRNA. Both CD44 mRNA are up-regulated by IL-1 alpha. Selective inhibition of CD44 exon 19 results i n enhanced hyaluronan internalization and smaller cell-associated matrices. Conclusion. The expression of a natural CD44 decoy-like receptor by articul ar chondrocytes modulates the function of this matrix receptor.