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Journal of Undergraduate Research

Keywords

HtrA1, Ddr2, MMP-13, osteoarthritis, sedc mice

College

Life Sciences

Department

Physiology and Developmental Biology

Abstract

In the present study, we report OA in a mouse model that, like the human families presented by Kannu et al., bears a heterozygous mutation in the Col2a1 gene but has a phenotypically normal skeleton.1 The mouse mutation was named sedc by Donahue et al. because when homozygous, it produces feature that resemble the most common clinical phenotypes of SED congenita in humans, including abnormal epiphyses, flattened vertebral bodies, and problems with the eyes and ears.2 The mutation consists of a single base pair substitution in exon 48 of the Col2a1 gene, which changes an arginine to a cysteine in the triple helical domain of the type II collagen protein. To look for signs of OA in the overtly normal heterozygous sedc (sedc/+) mice, we examined knee joint over the course of several months and found premature and progressive OA as demonstrated by loss of proteoglycans in the articular cartilage ECM, fibrillation of the articular surfaces, fissuring of the cartilage, and ultimately separation of uncalcified from calcified articular cartilage. Furthermore, we saw increased expression of HtrA1, a serine protease that is believed to degrade several different components of the PCM; of Ddr2, a cell surface receptor that binds native type II collagen as a ligand and upregulates MMP-13 in response; and of MMP- 13 itself, a matrix metalloproteinase that specifically digests type II collagen.3, 4 We conclude that the sedc/+ mouse is a useful model for OA in individuals with overtly normal skeletal structure who are predisposed to articular cartilage degeneration.

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