Abstract | OBJECTIVE: METHOD: RESULTS: Joint fluids from human patients after knee injury showed significantly enhanced levels of ARG- aggrecan compared to uninjured reference subjects. Similarly, synovial fluid ARG- aggrecan levels increased following surgically-induced joint instability in the rat MT model, which was significantly attenuated by orally dosing the animals with AGG-523, an aggrecanase specific inhibitor. CONCLUSIONS:
Aggrecanase-generated aggrecan fragments were rapidly released into human and rat joint fluids after injury to the knee and remained elevated over a prolonged period. Our findings in human and preclinical models strengthen the connection between aggrecanase activity in joints and knee injury and disease. The ability of a small molecule aggrecanase inhibitor to reduce the release of aggrecanase-generated aggrecan fragments into rat joints suggests that pharmacologic inhibition of aggrecanase activity in humans may be an effective treatment for slowing cartilage degradation following joint injury.
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Authors | P S Chockalingam, W Sun, M A Rivera-Bermudez, W Zeng, D R Dufield, S Larsson, L S Lohmander, C R Flannery, S S Glasson, K E Georgiadis, E A Morris |
Journal | Osteoarthritis and cartilage
(Osteoarthritis Cartilage)
Vol. 19
Issue 3
Pg. 315-23
(Mar 2011)
ISSN: 1522-9653 [Electronic] England |
PMID | 21163358
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved. |
Chemical References |
- Aggrecans
- Biomarkers
- Endopeptidases
- aggrecanase
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Topics |
- Aggrecans
(metabolism)
- Animals
- Biomarkers
(metabolism)
- Disease Models, Animal
- Endopeptidases
(metabolism)
- Enzyme-Linked Immunosorbent Assay
- Humans
- Knee Injuries
(enzymology)
- Rats
- Rats, Inbred Lew
- Synovial Fluid
(enzymology)
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