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Premature Osteoarthritis in the Temporomandibular Joint of Heterozygous Disproportionate Micromelia Mice
Author(s) -
Rees M. B.,
Ricks M. L.,
Falk D. J.,
Farrell J. T.,
Carr J. M.,
Williams D. T.,
Bridgewater L. C.,
Seegmiller R. E.,
Kooyman D. L.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.lb115
Subject(s) - osteoarthritis , cartilage , temporomandibular joint , proteoglycan , pathology , medicine , staining , western blot , chemistry , anatomy , gene , biochemistry , alternative medicine
A Col2a1 gene mutation disrupts collagen assembly and causes premature degeneration of knee articular cartilage in disproportionate micromelia ( Dmm ) mice. This study analyzed the temporomandibular joint (TMJ) in Dmm /+ mice to provide an animal model of TMJ osteoarthritis (OA) in humans. Dmm /+ mice and age‐matched controls were compared histologically at 2, 6, 9 and 12 months of age. Craniums were fixed in 4% paraformaldehyde, processed to paraffin sections, stained with Safranin‐O/Fast Green, and analyzed by light microscopy. OA severity was quantified using a modified Mankin scoring procedure. Activation of the unfolded protein stress response (UPR) was assayed by western blot. The Dmm /+ TMJ showed classic signs of OA as early as 6 months of age, whereas controls showed normal, intact cartilage. Mutant chondrocytes were clustered, leaving acellular regions in the matrix with decreased proteoglycan staining while pericellular regions showed increased staining. Dmm /+ TMJ showed increased levels of the proteins Ddr2, Mmp‐13, and HtrA1, which are associated with cartilage degradation. The levels of BiP and phospho‐elF2α, two markers of the UPR, were elevated at birth, suggesting that the UPR stress response may contribute to subsequent cartilage degeneration. This study demonstrates the utility of the Dmm/+ mouse TMJ as a viable model for TMJ OA in humans.