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Molecules (Basel, Switzerland) Aug 2019Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating -acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and... (Review)
Review
Galactosaminoglycans (GalAGs) are sulfated glycans composed of alternating -acetylgalactosamine and uronic acid units. Uronic acid epimerization, sulfation patterns and fucosylation are modifications observed on these molecules. GalAGs have been extensively studied and exploited because of their multiple biomedical functions. Chondroitin sulfates (CSs), the main representative family of GalAGs, have been used in alternative therapy of joint pain/inflammation and osteoarthritis. The relatively novel fucosylated chondroitin sulfate (FCS), commonly found in sea cucumbers, has been screened in multiple systems in addition to its widely studied anticoagulant action. Biomedical properties of GalAGs are directly dependent on the sugar composition, presence or lack of fucose branches, as well as sulfation patterns. Although research interest in GalAGs has increased considerably over the three last decades, perhaps motivated by the parallel progress of glycomics, serious questions concerning the effectiveness and potential side effects of GalAGs have recently been raised. Doubts have centered particularly on the beneficial functions of CS-based therapeutic supplements and the potential harmful effects of FCS as similarly observed for oversulfated chondroitin sulfate, as a contaminant of heparin. Unexpected components were also detected in CS-based pharmaceutical preparations. This review therefore aims to offer a discussion on (1) the current and potential therapeutic applications of GalAGs, including those of unique features extracted from marine sources, and (2) the potential drawbacks of this class of molecules when applied to medicine.
Topics: Acetylgalactosamine; Arthralgia; Chondroitin Sulfates; Humans; Osteoarthritis; Polysaccharides; Uronic Acids
PubMed: 31374852
DOI: 10.3390/molecules24152803 -
Frontiers in Genetics 2021Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans,... (Review)
Review
Glycosaminoglycans (GAGs) including chondroitin sulfate, dermatan sulfate, and heparan sulfate are covalently attached to specific core proteins to form proteoglycans, which are distributed at the cell surface as well as in the extracellular matrix. Proteoglycans and GAGs have been demonstrated to exhibit a variety of physiological functions such as construction of the extracellular matrix, tissue development, and cell signaling through interactions with extracellular matrix components, morphogens, cytokines, and growth factors. Not only connective tissue disorders including skeletal dysplasia, chondrodysplasia, multiple exostoses, and Ehlers-Danlos syndrome, but also heart and kidney defects, immune deficiencies, and neurological abnormalities have been shown to be caused by defects in GAGs as well as core proteins of proteoglycans. These findings indicate that GAGs and proteoglycans are essential for human development in major organs. The glycobiological aspects of congenital disorders caused by defects in GAG-biosynthetic enzymes including specific glysocyltransferases, epimerases, and sulfotransferases, in addition to core proteins of proteoglycans will be comprehensively discussed based on the literature to date.
PubMed: 34539746
DOI: 10.3389/fgene.2021.717535 -
Macromolecular Bioscience Mar 2022Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence...
Cartilage is a connective tissue which a limited capacity for healing and repairing. In this context, osteoarthritis (OA) disease may be developed with high prevalence in which the use of scaffolds may be a promising treatment. In addition, three-dimensional (3D) bioprinting has become an emerging additive manufacturing technology because of its rapid prototyping capacity and the possibility of creating complex structures. This study is focused on the development of nanocellulose-alginate (NC-Alg) based bioinks for 3D bioprinting for cartilage regeneration to which it is added chondroitin sulfate (CS) and dermatan sulfate (DS). First, rheological properties are evaluated. Then, sterilization effect, biocompatibility, and printability on developed NC-Alg-CS and NC-Alg-DS inks are evaluated. Subsequently, printed scaffolds are characterized. Finally, NC-Alg-CS and NC-Alg-DS inks are loaded with murine D1-MSCs-EPO and cell viability and functionality, as well as the chondrogenic differentiation ability are assessed. Results show that the addition of both CS and DS to the NC-Alg ink improves its characteristics in terms of rheology and cell viability and functionality. Moreover, differentiation to cartilage is promoted on NC-Alg-CS and NC-Alg-DS scaffolds. Therefore, the utilization of MSCs containing NC-Alg-CS and NC-Alg-DS scaffolds may become a feasible tissue engineering approach for cartilage regeneration.
Topics: Alginates; Animals; Bioprinting; Cartilage; Chondroitin; Dermatan Sulfate; Mice; Printing, Three-Dimensional; Regeneration; Tissue Engineering; Tissue Scaffolds
PubMed: 35029035
DOI: 10.1002/mabi.202100435 -
Biomolecules Aug 2015Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and... (Review)
Review
Proteoglycans (PGs) are glycosylated proteins of biological importance at cell surfaces, in the extracellular matrix, and in the circulation. PGs are produced and modified by glycosaminoglycan (GAG) chains in the secretory pathway of animal cells. The most common GAG attachment site is a serine residue followed by a glycine (-ser-gly-), from which a linker tetrasaccharide extends and may continue as a heparan sulfate, a heparin, a chondroitin sulfate, or a dermatan sulfate GAG chain. Which type of GAG chain becomes attached to the linker tetrasaccharide is influenced by the structure of the protein core, modifications occurring to the linker tetrasaccharide itself, and the biochemical environment of the Golgi apparatus, where GAG polymerization and modification by sulfation and epimerization take place. The same cell type may produce different GAG chains that vary, depending on the extent of epimerization and sulfation. However, it is not known to what extent these differences are caused by compartmental segregation of protein cores en route through the secretory pathway or by differential recruitment of modifying enzymes during synthesis of different PGs. The topic of this review is how different aspects of protein structure, cellular biochemistry, and compartmentalization may influence GAG synthesis.
Topics: Animals; Glycosaminoglycans; Golgi Apparatus; Humans; Membrane Transport Proteins; Secretory Pathway
PubMed: 26308067
DOI: 10.3390/biom5032003 -
Frontiers in Cell and Developmental... 2022
PubMed: 35757004
DOI: 10.3389/fcell.2022.941178 -
Matrix Biology : Journal of the... Oct 2018The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early... (Review)
Review
The content of proteoglycans (PGs) is low in the extracellular matrix (ECM) of vascular tissue, but increases dramatically in all phases of vascular disease. Early studies demonstrated that glycosaminoglycans (GAGs) including chondroitin sulfate (CS), dermatan sulfate (DS), keratan sulfate (KS) and heparan sulfate (HS) accumulate in vascular lesions in both humans and in animal models in areas of the vasculature that are susceptible to disease initiation (such as at branch points) and are frequently coincident with lipid deposits. Later studies showed the GAGs were covalently attached to specific types of core proteins that accumulate in vascular lesions. These molecules include versican (CSPG), biglycan and decorin (DS/CSPGs), lumican and fibromodulin (KSPGs) and perlecan (HSPG), although other types of PGs are present, but in lesser quantities. While the overall molecular design of these macromolecules is similar, there is tremendous structural diversity among the different PG families creating multiple forms that have selective roles in critical events that form the basis of vascular disease. PGs interact with a variety of different molecules involved in disease pathogenesis. For example, PGs bind and trap serum components that accumulate in vascular lesions such as lipoproteins, amyloid, calcium, and clotting factors. PGs interact with other ECM components and regulate, in part, ECM assembly and turnover. PGs interact with cells within the lesion and alter the phenotypes of both resident cells and cells that invade the lesion from the circulation. A number of therapeutic strategies have been developed to target specific PGs involved in key pathways that promote vascular disease. This review will provide a historical perspective of this field of research and then highlight some of the evidence that defines the involvement of PGs and their roles in the pathogenesis of vascular disease.
Topics: Animals; Extracellular Matrix; Glycosaminoglycans; Humans; Molecular Targeted Therapy; Proteoglycans; Signal Transduction; Vascular Diseases
PubMed: 29499356
DOI: 10.1016/j.matbio.2018.02.019 -
World Journal of Gastroenterology Jan 2016Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently... (Review)
Review
Proteoglycans are a group of molecules that contain at least one glycosaminoglycan chain, such as a heparan, dermatan, chondroitin, or keratan sulfate, covalently attached to the protein core. These molecules are categorized based on their structure, localization, and function, and can be found in the extracellular matrix, on the cell surface, and in the cytoplasm. Cell-surface heparan sulfate proteoglycans, such as syndecans, are the primary type present in healthy liver tissue. However, deterioration of the liver results in overproduction of other proteoglycan types. The purpose of this article is to provide a current summary of the most relevant data implicating proteoglycans in the development and progression of human and experimental liver cancer. A review of our work and other studies in the literature indicate that deterioration of liver function is accompanied by an increase in the amount of chondroitin sulfate proteoglycans. The alteration of proteoglycan composition interferes with the physiologic function of the liver on several levels. This article details and discusses the roles of syndecan-1, glypicans, agrin, perlecan, collagen XVIII/endostatin, endocan, serglycin, decorin, biglycan, asporin, fibromodulin, lumican, and versican in liver function. Specifically, glypicans, agrin, and versican play significant roles in the development of liver cancer. Conversely, the presence of decorin could potentially provide protective effects.
Topics: Agrin; Animals; Carcinoma, Hepatocellular; Glycosaminoglycans; Glypicans; Heparan Sulfate Proteoglycans; Humans; Liver Neoplasms; Liver Neoplasms, Experimental; Proteoglycans; Syndecan-1; Versicans
PubMed: 26755884
DOI: 10.3748/wjg.v22.i1.379 -
The Journal of Histochemistry and... Feb 2021The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear... (Review)
Review
The six mammalian glycosaminoglycans (GAGs), chondroitin sulfate, dermatan sulfate, heparin, heparan sulfate, hyaluronan, and keratan sulfate, are linear polysaccharides. Except for hyaluronan, they are sulfated to various extent, and covalently attached to proteins to form proteoglycans. GAGs interact with growth factors, morphogens, chemokines, extracellular matrix proteins and their bioactive fragments, receptors, lipoproteins, and pathogens. These interactions mediate their functions, from embryonic development to extracellular matrix assembly and regulation of cell signaling in various physiological and pathological contexts such as angiogenesis, cancer, neurodegenerative diseases, and infections. We give an overview of GAG-protein interactions (i.e., specificity and chemical features of GAG- and protein-binding sequences), and review the available GAG-protein interaction networks. We also provide the first comprehensive draft of the GAG interactome composed of 832 biomolecules (827 proteins and five GAGs) and 932 protein-GAG interactions. This network is a scaffold, which in the future should integrate structures of GAG-protein complexes, quantitative data of the abundance of GAGs in tissues to build tissue-specific interactomes, and GAG interactions with metal ions such as calcium, which plays a major role in the assembly of the extracellular matrix and its interactions with cells. This contextualized interactome will be useful to identify druggable GAG-protein interactions for therapeutic purpose.
Topics: Animals; Extracellular Matrix Proteins; Glycosaminoglycans; Humans
PubMed: 32757871
DOI: 10.1369/0022155420946403