Attenuation of osteoarthritis progression by reduction of discoidin domain receptor 2 in mice.
Arthritis Rheum
; 62(9): 2736-44, 2010 Sep.
Article
em En
| MEDLINE
| ID: mdl-20518074
ABSTRACT
OBJECTIVE:
To investigate whether the reduction of discoidin domain receptor 2 (DDR-2), a cell membrane tyrosine kinase receptor for native type II collagen, attenuates the progression of articular cartilage degeneration in mouse models of osteoarthritis (OA).METHODS:
Double-heterozygous (type XI collagen-deficient [Col11a1(+/-)] and Ddr2-deficient [Ddr2(+/-)]) mutant mice were generated. Knee joints of Ddr2(+/-) mice were subjected to microsurgical destabilization of the medial meniscus. Conditions of the articular cartilage from the knee joints of the double-heterozygous mutant and surgically treated mice were examined by histology, evaluated using a modified Mankin scoring system, and characterized by immunohistochemistry.RESULTS:
The rate of progressive degeneration in knee joints was dramatically reduced in the double-heterozygous mutant mice compared with that in the type XI collagen-deficient mice. The progression in the double-heterozygous mutant mice was delayed by â¼6 months. Following surgical destabilization of the medial meniscus, the progressive degeneration toward OA was dramatically delayed in the Ddr2(+/-) mice compared with that in their wild-type littermates. The articular cartilage damage present in the knee joints of the mice was directly correlated with the expression profiles of DDR-2 and matrix metalloproteinase 13.CONCLUSION:
Reduction of DDR-2 expression attenuates the articular cartilage degeneration of knee joints induced either by type XI collagen deficiency or by surgical destabilization of the medial meniscus.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
/
Receptores Mitogênicos
/
Receptores Proteína Tirosina Quinases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Arthritis Rheum
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Estados Unidos