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
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