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.


CONCLUSIONS
CD44 expression is needed for maintenance of cartilage homeostasis.
Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
G
G
Chow
J J
JJ
Nietfeld
C B
CB
Knudson
W
W
Knudson
D000818:Animals; D015153:Blotting, Western; D002358:Cartilage, Articular / Q000187:drug effects / Q000473:pathology*; D002417:Cattle; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D018960:Hyaluronan Receptors / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D010003:Osteoarthritis / Q000473:pathology; D013873:Thionucleotides / Q000235:genetics / Q000494:pharmacology; D013997:Time Factors
D018960:Hyaluronan Receptors; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides