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Experimental arthritis

Oral aggrecanase inhibitor may slow postinjury cartilage breakdown

Nature Reviews Rheumatology volume 7, page 131 (2011)Cite this article

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AGG-523, an aggrecanase inhibitor, reduces synovial fluid levels of Ala–Arg–Gly-aggrecan (a major cartilage matrix breakdown product) in a rat model of knee injury, new findings show. “Our study suggests the potential of postinjury aggrecanase inhibition to stop or slow down immediate cartilage degradation as well as development of osteoarthritis years after injury in humans,” explains lead investigator, Priya Chockalingam.

The researchers developed a highly sensitive and specific enzyme-linked immunosorbent assay, using commercially available reagents, which revealed elevated levels of Ala–Arg–Gly-aggrecan in synovial fluid from animals and humans with knee injury. Levels of this fragment in human knee synovial fluid increased by an average of 13.6-fold in the 12 weeks after cruciate ligament rupture and 8.1-fold after meniscal injury. Although Ala–Arg–Gly-aggrecan levels then declined, they were still elevated 1 year after injury—by an average of 3.3-fold and 1.4-fold, respectively.

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ORIGINAL RESEARCH PAPER

  1. Chockalingam, P. S. et al. Elevated aggrecanase activity in a rat model of joint injury is attenuated by an aggrecanase specific inhibitor. Osteoarthr. Cartil. doi:10.1016/j.joca.2010.12.004

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  1. Paul J. Simpson
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Simpson, P. Oral aggrecanase inhibitor may slow postinjury cartilage breakdown. Nat Rev Rheumatol 7, 131 (2011). https://doi.org/10.1038/nrrheum.2011.10

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  • DOI: https://doi.org/10.1038/nrrheum.2011.10

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