Structural Variations in Articular Cartilage Matrix Are Associated with Early-Onset Osteoarthritis in the Spondyloepiphyseal Dysplasia Congenita (Sedc) Mouse
Autor: | Shaela A. Avery, Christopher R. Cunningham, David W. Macdonald, Ryan S. Squires, Jason Adams, Nicholas B. Heimann, Melissa Baker, Robert E. Seegmiller, David L. Kooyman |
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Rok vydání: | 2013 |
Předmět: |
Cartilage
Articular Pathology spondyloepiphyseal dysplasia congenita (sedc) Dwarfism Osteoarthritis Matrix (biology) lcsh:Chemistry Extracellular matrix Mice 0302 clinical medicine proteoglycan animal model of osteoarthritis Col2a1 type II collagen articular cartilage extracellular matrix lcsh:QH301-705.5 Spectroscopy 0303 health sciences Chemistry General Medicine Computer Science Applications medicine.anatomical_structure Spondyloepiphyseal dysplasia congenita musculoskeletal diseases medicine.medical_specialty Type II collagen Mice Transgenic Osteochondrodysplasias Article Catalysis Chondrocyte Inorganic Chemistry 03 medical and health sciences Chondrocytes medicine Animals Physical and Theoretical Chemistry Collagen Type II Molecular Biology 030304 developmental biology Cartilage Organic Chemistry medicine.disease lcsh:Biology (General) lcsh:QD1-999 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences; Volume 14; Issue 8; Pages: 16515-16531 International Journal of Molecular Sciences, Vol 14, Iss 8, Pp 16515-16531 (2013) International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
DOI: | 10.3390/ijms140816515 |
Popis: | 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. |
Databáze: | OpenAIRE |
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