RESEARCH ARTICLE
Biosynthesis of Natural and Hyperelongated Chondroitin Sulfate Glycosaminoglycans: New Insights into an Elusive Process
Peter J. Little*, a, b, c, Mandy L Ballingera, Micah L Burcha, c, Narin Osmana, b
Article Information
Identifiers and Pagination:
Year: 2008Volume: 2
First Page: 135
Last Page: 142
Publisher ID: TOBIOCJ-2-135
DOI: 10.2174/1874091X00802010135
Article History:
Received Date: 1/9/2008Revision Received Date: 10/9/2008
Acceptance Date: 14/9/2008
Electronic publication date: 18/9/2008
Collection year: 2008
open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.
Abstract
Proteoglycans are important components of the extracellular matrix of all tissues. Proteoglycans are comprised of a core protein and one or more covalently attached glycosaminoglycan (GAG) chains. The major chondroitin sulfate (CS) and dermatan sulfate (DS) proteoglycans are aggrecan, versican, biglycan and decorin. Cells synthesize GAGs of natural or basal lengths and the GAG chains are subject to considerable growth factor, hormonal and metabolic regulation to yield longer GAG chains with altered structure and function. The mechanism by which the CS/DS GAG chains are polymerized is unknown. Recent work has identified several monosaccharide transferases which when co-expressed yield GAG polymers and the length of the polymers depends upon the pair of enzymes coexpressed. The further extension of these chains is regulated by signaling pathways. Inhibition of these latter pathways may be a therapeutic target to prevent the elongation which is associated with increased binding of atherogenic lipids and the disease process of atherosclerosis.
