Cathepsin K inhibition reduces CTXII levels and joint pain in the guinea pig model of spontaneous osteoarthritis.
Osteoarthritis Cartilage
; 18(10): 1355-7, 2010 Oct.
Article
em En
| MEDLINE
| ID: mdl-20692355
ABSTRACT
Cathepsin K is a cysteine proteinase which is believed to contribute to osteoarthritis (OA) pathogenesis. This brief report evaluates the effect of the novel selective cathepsin K inhibitor AZ12606133 on cartilage metabolism in the Dunkin-Hartley guinea pig model of spontaneous OA. In parallel, electrophysiological studies were performed to determine whether acute and chronic treatment with the cathepsin K inhibitor could alter joint nociception. Acute treatment of OA knees with AZ12606133 had no effect on joint afferent nerve activity; however, prolonged (1 month) administration of the cathepsin K inhibitor delivered via a chronically implanted osmotic pump significantly reduced mechanosensitivity in response to both non-noxious and noxious joint movements. Urinal concentrations of the cartilage breakdown products cross-linked C-telopeptides of type II collagen (CTXII) were also reduced by chronic cathepsin K inhibition. These data suggest that prolonged AZ12606133 administration can reduce cartilage turnover and joint nociception in the Dunkin-Hartley guinea pig model of spontaneous OA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Dor
/
Fragmentos de Peptídeos
/
Artrite Experimental
/
Colágeno Tipo II
/
Catepsina K
Tipo de estudo:
Etiology_studies
Limite:
Animals
Idioma:
En
Revista:
Osteoarthritis Cartilage
Assunto da revista:
ORTOPEDIA
/
REUMATOLOGIA
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Canadá