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Related Experiment Videos

Antisense oligonucleotides to the integrin receptor subunit alpha(5) decrease fibronectin fragment mediated cartilage

G A Homandberg1, V Costa, V Ummadi

  • 1Department of Biochemistry, Rush Medical College at Rush-Presbyterian-St Luke's Medical Center, 1653 West Congress Parkway, Chicago, Illinois 60612-3864, USA. ghomandb@rush.edu

Osteoarthritis and Cartilage
|May 25, 2002
PubMed
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Antisense oligonucleotide targeting the integrin alpha(5) subunit inhibited fibronectin fragment-induced cartilage degradation and suppressed proteoglycan synthesis. This suggests alpha(5)beta(1) integrin plays a role in chondrolytic activities.

Area of Science:

  • Biochemistry
  • Cell Biology
  • Integrin Signaling

Background:

  • Fibronectin fragments (Fn-f) contribute to cartilage degradation.
  • The classical fibronectin receptor, integrin alpha(5)beta(1), is a potential mediator of these effects.

Purpose of the Study:

  • To investigate the role of the integrin alpha(5) subunit in fibronectin fragment-induced chondrolytic activities.
  • To determine if blocking alpha(5) subunit expression affects cartilage catabolism.

Main Methods:

  • Bovine chondrocytes and cartilage explants were treated with antisense oligonucleotide (ASO) targeting the alpha(5) subunit.
  • mRNA and protein expression of alpha(5) were analyzed using rtPCR and Western blotting.
  • Effects on proteoglycan degradation, synthesis, and protein synthesis suppression by Fn-f were assessed.

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Main Results:

  • ASO significantly reduced alpha(5) mRNA and protein expression.
  • ASO partially reversed Fn-f-mediated suppression of proteoglycan and protein synthesis.
  • ASO suppressed Fn-f-induced proteoglycan degradation in a dose-dependent and reversible manner.

Conclusions:

  • The alpha(5) integrin subunit is implicated in fibronectin fragment-mediated cartilage degradation.
  • These findings support a role for the alpha(5)beta(1) integrin in chondrolytic pathways.