Role of collagen type II and perlecan in skeletal development.
The cartilage extracellular matrix is composed of a dense collagen network that entraps a range of other specialized proteins important for the proper formation and function of the tissue. Loss of two abundant cartilage components, type II collagen and perlecan, has drastic effects on skeletal development. Both collagen II and perlecan mutants have severe and lethal chondrodysplasia characterized by disorganized growth plate, lack of collagen network, defective endochondral bone formation, and abnormal intervertebral disk development. To test whether the reduced collagen density in the perlecan-null cartilage is due to enhanced activity of collagen-degrading proteinases, we have analyzed gelatinase expression and activity in the mutant tissue. Immunohistochemical analysis revealed a weak, but clear, expansion of MMP-9 deposition into the hypertrophic zone of the perlecan-null growth plate. However, in situ and SDS-PAGE zymography showed that the activity of gelatinases (MMP-2 and MMP-9) is not altered in perlecan-null cartilage, suggesting that they are not primarily linked to the reduced fibrillar network observed in the mutant. Likewise, intercrossing of perlecan mutants onto an MMP-9-null background could not rescue the ultrastructural abnormalities of the perlecan-deficient cartilage.
Gustafsson
Erika
E
Department of Experimental Pathology, Lund University, 22185 Lund, Sweden.
Aszodi
Attila
A
Ortega
Nathalie
N
Hunziker
Ernst B
EB
Denker
Hans-Werner
HW
Werb
Zena
Z
Fassler
Reinhard
R
D000818:Animals; D001842:Bone and Bones / Q000033:anatomy & histology / Q000196:embryology*; D002356:Cartilage / Q000196:embryology / Q000648:ultrastructure; D024043:Collagen Type II / Q000235:genetics / Q000502:physiology*; D004622:Embryo, Mammalian / Q000033:anatomy & histology / Q000201:enzymology / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000648:ultrastructure; D024022:Fibrillar Collagens / Q000648:ultrastructure; D018093:Gelatinases / Q000378:metabolism; D019812:Heparan Sulfate Proteoglycans / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D010009:Osteochondrodysplasias / Q000209:etiology; D010012:Osteogenesis
D024043:Collagen Type II; D024022:Fibrillar Collagens; D019812:Heparan Sulfate Proteoglycans; C071927:perlecan; D018093:Gelatinases