Title
Chondrocyte rather than osteoblast conversion of vascular cells underlies medial calcification in uremic rats
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Publication type
article
Publication
Dallas, Tex. ,
Subject
Human medicine
Source (journal)
Arteriosclerosis, thrombosis, and vascular biology / American Heart Association. - Dallas, Tex., 1995, currens
Volume/pages
30(2010) :9 , p. 1741-1750
ISSN
1079-5642
1524-4636
ISI
000281135900011
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Objective: To investigate cell biological changes in calcified aortas of rats that experienced chronic renal failure. Methods and Results: Vascular smooth muscle cells have the potential to transdifferentiate to either chondrocytes or osteoblasts, depending on the molecular pathways that are stimulated. Uremia-related medial calcification was induced by feeding rats an adenine low-protein diet for 4 weeks. Aortic calcification was evaluated biochemically and histochemically and with in vivo microcomputed tomographic scanning. Immunohistochemistry and RT-PCR were applied to analyze the time-dependent aortic expression of molecules involved in the segregation between the chondrocyte versus osteoblast differentiation pathway. After 4 weeks, 85% of the uremic rats had developed distinct aortic medial calcification, which increased to severely calcified lesions during further follow-up. The calcification process was accompanied by a significant time-dependent increase in the expression of the chondrocyte-specific markers sex determining region Y-box 9 (sox9), collagen II, and aggrecan and a nonsignificant trend toward enhanced core binding factor alpha 1 (cbfa1), and collagen I. The expression of the osteoblast marker osterix and both lipoprotein receptorrelated protein 6 and [beta]-catenin, molecules of the wingless-type MMTV integration site family member (Wnt)/[beta]-catenin pathway induced during osteoblast differentiation, was suppressed. Conclusion: In the aorta of uremic rats, medial smooth muscle cells acquire a chondrocyte rather than osteoblast phenotype during the calcification process.
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