Dysplastic histogenesis of cartilage growth plate by alteration of sulphation pathway: a transgenic model.
Mutations in the diastrophic dysplasia sulphate transporter (dtdst) gene causes different forms of chondrodysplasia in the human. The generation of a knock-in mouse strain with a mutation in dtdst gene provides the basis to study developmental dynamics in the epiphyseal growth plate and long bone growth after impairment of the sulphate pathway. Our microscopical and histochemical data demonstrate that dtdst gene impairment deeply affects tissue organization, matrix structure, and cell differentiation in the epiphyseal growth plate. In mutant animals, the height of the growth plate was significantly reduced, according to a concomitant decrease in cell density and proliferation. Although the pathway of chondrocyte differentiation seemed complete, alteration in cell morphology compared to normal counterparts was detected. In the extracellular matrix, it we observed a dramatic decrease in sulphated proteoglycans, alterations in the organization of type II and type X collagen fibers, and premature onset of mineralization. These data confirm the crucial role of sulphate pathway in proteoglycan biochemistry and suggest that a disarrangement of the extracellular matrix may be responsible for the development of dtdts cartilage dysplasia. Moreover, we corroborated the concept that proteoglycans not only are structural components of the cartilage architecture, but also play a dynamic role in the regulation of chondrocyte growth and differentiation.
Cornaglia
Antonia Icaro
AI
Department of Experimental Medicine, Histology and Embryology Unit, University of Pavia, Pavia, Italy. icaro@unipv.it
Casasco
Andrea
A
Casasco
Marco
M
Riva
Federica
F
Necchi
Vittorio
V
D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D001692:Biological Transport; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism / Q000648:ultrastructure; D006132:Growth Plate / Q000002:abnormalities* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D010009:Osteochondrodysplasias / Q000235:genetics / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism; D000076988:Sulfate Transporters; D013431:Sulfates / Q000378:metabolism*
D027321:Anion Transport Proteins; D011509:Proteoglycans; C513264:Slc26a2 protein, mouse; D000076988:Sulfate Transporters; D013431:Sulfates