Antisense inhibition of chondrocyte CD44 expression leading to cartilage chondrolysis

Objective To better define critical functions of the hyaluronan receptor CD44 in cartilage. Methods Articular chondrocytes and cartilage tissue slices were treated with CD44 sequence-specific antisense phosphorothioate oligonucleotides. CD44 expression was probed by immunofluorescence microscopy, enzyme-linked immunosorbent assay, and Western blotting. Results Antisense oligonucleotides demonstrated a dose- and time-dependent inhibition of CD44 protein expression; negative controls showed no effect. Similar to osteoarthritic cartilage, antisense-treated cartilage slices displayed a near-total loss of stainable proteoglycan-rich matrix. Conclusion CD44 expression is needed for maintenance of cartilage homeostasis.