Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice.
Osteoarthritis Cartilage
; 18(1): 88-96, 2010 Jan.
Article
de En
| MEDLINE
| ID: mdl-19932218
ABSTRACT
OBJECTIVE:
To characterize the in vivo role epiphycan (Epn) has in cartilage development and/or maintenance.METHODS:
Epn-deficient mice were generated by disrupting the Epn gene in mouse embryonic stem cells. Epn/biglycan (Bgn) double-deficient mice were produced by crossing Epn-deficient mice with Bgn-deficient mice. Whole knee joint histological sections were stained using van Gieson or Fast green/Safranin-O to analyze collagen or proteoglycan content, respectively. Microarray analysis was performed to detect gene expression changes within knee joints.RESULTS:
Epn-deficient and Epn/Bgn double-deficient mice appeared normal at birth. No significant difference in body weight or femur length was detected in any animal at 1 month of age. However, 9-month Epn/Bgn double-deficient mice were significantly lighter and had shorter femurs than wild type mice, regardless of gender. Male Epn-deficient mice also had significantly shorter femurs than wild type mice at 9 months. Most of the deficient animals developed osteoarthritis (OA) with age; the onset of OA was observed earliest in Epn/Bgn double-deficient mice. Message RNA isolated from Epn/Bgn double-deficient knee joints displayed increased matrix protein expression compared with wild type mice, including other small leucine-rich proteoglycan (SLRP) members such as asporin, fibromodulin and lumican.CONCLUSION:
Similar to other previously studied SLRPs, EPN plays an important role in maintaining joint integrity. However, the severity of the OA phenotype in the Epn/Bgn double-deficient mouse suggests a synergy between these two proteins. These data are the first to show a genetic interaction involving class I and class III SLRPs in vivo.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Protéoglycanes
/
Gonarthrose
/
Articulation du genou
Limites:
Animals
Langue:
En
Journal:
Osteoarthritis Cartilage
Sujet du journal:
ORTOPEDIA
/
REUMATOLOGIA
Année:
2010
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique