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J Rheumatol. 2012 Mar;39(3):583-93. doi: 10.3899/jrheum.110971. Epub 2012 Feb 1.

Aberrant chondrocyte hypertrophy and activation of β-catenin signaling precede joint ankylosis in ank/ank mice.

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  • 1Pathology and Laboratory Medicine, Mount Sinai Hospital, Canada.

Abstract

OBJECTIVE:

We assessed the role of Ank in the maintenance of postnatal articular cartilage using the ank/ank mouse (mice homozygous for progressive ankylosis).

METHODS:

We analyzed ank/ank mice and wild-type littermates (8, 12, and 18 weeks old). Sections from decalcified, paraffin-embedded joints were stained with hematoxylin and eosin. Articular chondrocyte size and cartilage thickness were determined using morphometric methods. Immuno-histochemical staining was performed with anticollagen X, antitissue nonspecific alkaline phosphatase (TNAP), and anti-ß-catenin antibodies on fixed joint sections. Axin2 expression in paw joint lysates in wild-type versus ank/ank mice were compared using Western blot analysis.

RESULTS:

In all age groups of normal mice studied, calcified cartilage (CC) chondrocyte areas were significantly larger than those of uncalcified cartilage (UC) chondrocytes. However, similar chondrocyte areas (UC vs CC) were found in 12-week and 18-week-old ank/ank mice, indicating that hypertrophic chondrocytes were present in the UC of these mutant mice. The ank/ank mice showed an increase in CC thickness. The ank/ank UC hypertrophic chondrocytes showed diffuse immuno-reactivity for collagen X and TNAP. Increased ß-catenin activation was demonstrated by nuclear localization of ß-catenin staining in ank/ank chondrocytes. Axin2 expression from paw lysates was downregulated in ank/ank mice.

CONCLUSION:

We identified a previously unrecognized phenotype in the articular cartilage of ank/ank mice: collagen X-positive hypertrophic chondrocytes in the UC. It is possible that consequent to downregulation of axin2 expression, ß-catenin signaling was activated, leading to accelerated chondrocyte maturation and eventual ankylosis in ank/ank joints. Our studies shed new light on the contribution of a key signaling pathway in this model of joint ankylosis.

PMID:
22298904
[PubMed - indexed for MEDLINE]
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