Osteoarthritis (OA) is a degenerative joint disease that affects more than 60% of Americans 65 and older. Because human subjects and samples are not readily available for research, animal models are an invaluable resource for the study of OA. Disproportionate micromelia (Dmm) is one such model that develops OA early in life due to a deletion in the c-propeptide of the Col2a1 gene. Light microscope analysis of the articular cartilage in Dmm has been completed, but is insufficient to show the cellular effects of the deletion mutation in Dmm in adequate detail. The present study explores the changes that occur in the rough endoplasmic reticulum (ER) of chondrocytes in the articular cartilage of Dmm heterozygous mutants (D/+). Immunohistochemical analysis in Dmm has shown that type II collagen is absent extracellularly in articular cartilage of Dmm homozygous mutants and reduced in the heterozygotes. Because preprocollagens are processed through the endoplasmic reticulum (ER), it has been hypothesized that due to improper folding this mutation prevents newly synthesized collagen from leaving the ER, as a result large dilations are seen in the ER of Dmm mice. Furthermore, matrix area fractions should be reduced in the D/+ group if indeed type II collagen is not secreted. Data collected indicated that at 4 months and older, large distensions in the ER disappear. At age 0 months, there is significant dilation in the ER of the D/+ (p=.0013), and at .75 months significant dilation is also observed (p=.0063). In pooled age groups, the D/+ has a 1.77% greater ER fraction than the +/+ (p=.0022). The matrix area fraction was also significantly lower in the D/+ compared to the +/+ (p=.0037). Apoptosis was prominent in older ages, but did not appear to be different between +/+ and D/+ mice. Because decreased matrix and dilation of ER have been documented in OA, Dmm is a good model of OA that can be further used to study the molecular changes and deficiencies that occur in the pathogenesis of OA.
College and Department
Life Sciences; Physiology and Developmental Biology
BYU ScholarsArchive Citation
Smaldone, Crystal Noelle, "Cellular and Matrix Changes in Articular Cartilage of the Disproportionate micromelia Mouse Model of Osteoarthritis" (2008). All Theses and Dissertations. 1636.
osteoarthritis, cartilage, Disproportionate micromelia (Dmm), dwarfism, collagen, Col2a1