Inhibition of hyaluronan export reduces collagen degradation in interleukin-1 treated cartilage.

Arthritis Research & Therapy
Barthold Deiters, P Prehm

Abstract

Osteoarthrosis is characterized by cartilage erosion, proteolysis of aggrecan and collagen, and disturbed rates of synthesis of aggrecan and hyaluronan by chondrocytes, with hyaluronan over-production being an early reaction. We considered that inhibition of hyaluronan export might prevent subsequent proteoglycan loss and collagen degradation. To test this hypothesis, we studied a tissue culture model using bovine cartilages explants activated with IL-1alpha to induce osteoarthritic reactions using the phosphodiesterase-5 inhibitors tadalafil, zaprinast and vardenafil. These drugs inhibited hyaluronan export, but they did not inhibit hyaluronan synthase activity. Simultaneously, they inhibited proteoglycan loss and collagen degradation, but not their synthesis. They also reduced the release of gelatinases into the culture media and diffusion of the indicator protein horseradish peroxidase through the cartilage explants. The mechanism of action of these compounds may be through inhibition of hyaluronan exporter multidrug resistance-associated protein 5 (MRP5), because the effective drug concentrations were much higher than required for phosphodiesterase-5 inhibition and intracellular cGMP accumulation. Inhibition of hyaluronan o...Continue Reading

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Citations

Jul 26, 2013·Arthritis Research & Therapy·Nicholas PeakeTina T Chowdhury
Sep 20, 2008·Journal of Cellular Biochemistry·Katharina MonzPeter Prehm
Sep 20, 2011·Journal of Cellular Biochemistry·Jelena JoergesPeter Prehm
Jul 29, 2010·Journal of Cellular Biochemistry·Daniel HagenfeldPeter Prehm
Sep 18, 2010·Molecular Nutrition & Food Research·Dennis StrackePeter Prehm
Jan 13, 2015·Journal of Orthopaedic Surgery and Research·Kiriakos DaniilidisPeter Prehm
Aug 27, 2015·Biochemical and Biophysical Research Communications·N J PeakeT T Chowdhury
Aug 28, 2013·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Peter Prehm
Jan 12, 2010·Experimental Cell Research·Natalie K Thomas, Tracey J Brown

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