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Osteoarthritis Cartilage. 2010 Jan;18(1):88-96. doi: 10.1016/j.joca.2009.11.006. Epub 2009 Nov 18.

Phenotypic characterization of epiphycan-deficient and epiphycan/biglycan double-deficient mice.

Author information

1
Texas A&M University System Health Science Center, Albert B Alkek Institute of Biosciences and Technology, Center for Extracellular Matrix Biology, Houston, TX 77030, USA.

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.

PMID:
19932218
PMCID:
PMC3013283
DOI:
10.1016/j.joca.2009.11.006
[Indexed for MEDLINE]
Free PMC Article
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