Antisense inhibition of chondrocyte CD44 expression leading to cartilage chondrolysis
Open Access
- 1 August 1998
- journal article
- basic science
- Published by Wiley in Arthritis & Rheumatism
- Vol. 41 (8) , 1411-1419
- https://doi.org/10.1002/1529-0131(199808)41:8<1411::aid-art10>3.0.co;2-z
Abstract
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.Keywords
This publication has 37 references indexed in Scilit:
- Selective suppression of CD44 in keratinocytes of mice bearing an antisense CD44 transgene driven by a tissue-specific promoter disrupts hyaluronate metabolism in the skin and impairs keratinocyte proliferation.Genes & Development, 1997
- Quantitative Antisense Dose-Response Relationships: Mathematical Modeling of Antisense Action Under Steady-State ConditionsAntisense and Nucleic Acid Drug Development, 1997
- Aggrecan is degraded by matrix metalloproteinases in human arthritis. Evidence that matrix metalloproteinase and aggrecanase activities can be independent.Journal of Clinical Investigation, 1996
- Increased Expression of CD44 in Bovine Articular Chondrocytes by Catabolic Cellular MediatorsJournal of Biological Chemistry, 1995
- Antisense oligonucleotides, a novel tool for the control of cytokine effects on human cartilage. focus on interleukins 1 and 6 and proteoglycan synthesisArthritis & Rheumatism, 1994
- ERM family members as molecular linkers between the cell surface glycoprotein CD44 and actin-based cytoskeletons.The Journal of cell biology, 1994
- Repair of articular cartilage injury following intra‐articular chymopapain‐induced matrix proteoglycan lossJournal of Orthopaedic Research, 1993
- Use of Antisense Oligomers to Study the Role of c‐jun in G1 ProgressionaAnnals of the New York Academy of Sciences, 1992
- Phosphorothioate oligodeoxynucleotides—anti-sense inhibitors of gene expression?Pharmacology & Therapeutics, 1991
- Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4Nature, 1970