Structural variations in articular cartilage matrix are associated with early-onset osteoarthritis in the spondyloepiphyseal dysplasia congenita (sedc) mouse.

Abstract

Heterozgyous spondyloepiphyseal dysplasia congenita (sedc/+) mice expressing a missense mutation in col2a1 exhibit a normal skeletal morphology but early-onset osteoarthritis (OA). We have recently examined knee articular cartilage obtained from homozygous (sedc/sedc) mice, which express a Stickler-like phenotype including dwarfism. We examined sedc/sedc mice at various levels to better understand the mechanistic process resulting in OA. Mutant sedc/sedc, and control (+/+) cartilages were compared at two, six and nine months of age. Tissues were fixed, decalcified, processed to paraffin sections, and stained with hematoxylin/eosin and safranin O/fast green. Samples were analyzed under the light microscope and the modified Mankin and OARSI scoring system was used to quantify the OA-like changes. Knees were stained with 1C10 antibody to detect the presence and distribution of type II collagen. Electron microscopy was used to study chondrocyte morphology and collagen fibril diameter. Compared with controls, mutant articular cartilage displayed decreased fibril diameter concomitant with increases in size of the pericellular space, Mankin and OARSI scores, cartilage thickness, chondrocyte clustering, proteoglycan staining and horizontal fissuring. In conclusion, homozygous sedc mice are subject to early-onset knee OA. We conclude that collagen in the mutant's articular cartilage (both heterozygote and homozygote) fails to provide the normal meshwork required for matrix integrity and overall cartilage stability.

• Authors: David W Macdonald, Ryan S Squires, Shaela A Avery, Jason Adams, Melissa Baker, Christopher R Cunningham, Nicholas B Heimann, David L Kooyman, Robert E Seegmiller
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 14 Issue 8 Pg. 16515-31 (Aug 09 2013) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 23939426 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Col2a1 protein, mouse
• Collagen Type II

Topics

• Animals
• Cartilage, Articular (anatomy & histology, physiology)
• Chondrocytes (cytology)
• Collagen Type II (analysis, genetics)
• Dwarfism (complications, genetics)
• Mice
• Mice, Transgenic
• Osteoarthritis (genetics)
• Osteochondrodysplasias (congenital, genetics)