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Biomolecules Dec 2020Glycosaminoglycans are native components of the extracellular matrix that drive cell behavior and control the microenvironment surrounding cells, making them promising... (Review)
Review
Glycosaminoglycans are native components of the extracellular matrix that drive cell behavior and control the microenvironment surrounding cells, making them promising therapeutic targets for a myriad of diseases. Recent studies have shown that recapitulation of cell interactions with the extracellular matrix are key in tissue engineering, where the aim is to mimic and regenerate endogenous tissues. Because of this, incorporation of glycosaminoglycans to drive stem cell fate and promote cell proliferation in engineered tissues has gained increasing attention. This review summarizes the role glycosaminoglycans can play in tissue engineering and the recent advances in their use in these constructs. We also evaluate the general trend of research in this niche and provide insight into its future directions.
Topics: Animals; Biocompatible Materials; Cell Communication; Cell Differentiation; Cell Proliferation; Extracellular Matrix; Glycosaminoglycans; Humans; Stem Cells; Tissue Engineering; Tissue Scaffolds
PubMed: 33383795
DOI: 10.3390/biom11010029 -
Current Opinion in Structural Biology Jun 2018Glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate are linear glycans, which when attached to protein backbones form... (Review)
Review
Glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin/dermatan sulfate, and keratan sulfate are linear glycans, which when attached to protein backbones form proteoglycans. GAGs are essential components of the extracellular space in metazoans. Extensive modifications of the glycans such as sulfation, deacetylation and epimerization create structural GAG motifs. These motifs regulate protein-protein interactions and are thereby repsonsible for many of the essential functions of GAGs. This review focusses on recent genetic approaches to characterize GAG motifs and their function in defined signaling pathways during development. We discuss a coding approach for GAGs that would enable computational analyses of GAG sequences such as alignments and the computation of position weight matrices to describe GAG motifs.
Topics: Extracellular Matrix Proteins; Fibroblast Growth Factors; Glycosaminoglycans; Humans; Hyaluronic Acid; Molecular Structure; Nerve Growth Factor; Nerve Tissue Proteins; Signal Transduction; Structure-Activity Relationship
PubMed: 29579579
DOI: 10.1016/j.sbi.2018.03.011 -
Methods in Molecular Biology (Clifton,... 2022Glycosaminoglycans (GAGs) are heterogeneous biomacromolecules made by all animal cells with overlapping molecular weight and high negative charge densities, which make...
Glycosaminoglycans (GAGs) are heterogeneous biomacromolecules made by all animal cells with overlapping molecular weight and high negative charge densities, which make thorough separation of different types of GAGs and elimination of all GAG-binding proteins difficult. Even with the constant challenge of quality control, chondroitin sulfate, dermatan sulfate, heparan sulfate, and heparin glycosaminoglycans (GAGs) have been used as nutraceuticals and modern drugs for many years worldwide. Testing galactosamine in heparin has been added to the USP monograph after contaminated heparin event, but the general monosaccharide composition analysis has not been developed for GAG quality control purposes. Using a PCR-facilitated hydrolysis assay, the hydrolyzed GAG saccharides were labeled with 1-phenyl-3-methyl-5-pyrazolone (PMP) and quantified by high performance liquid chromatography (HPLC) coupled with mass spectrometry (MS). Glucosamine was found in both chondroitin sulfate and dermatan sulfate whereas galactosamine was observed in both heparan sulfate and heparin, indicating the cross contamination among different types of GAGs. Moreover, fucose was detected in chondroitin sulfate, dermatan sulfate, and heparan sulfate, and both fucose and mannose were detected in chondroitin sulfate, suggesting the co-presence of other types of glycans or novel fucosylated GAG structures. Furthermore, both the amount and structure of acid-resistant disaccharides provide distinguishable features for each type of GAGs at the same hydrolysis condition. Thus, monosaccharide analysis provides a practical and quantitative way for GAG quality control.
Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Fucose; Galactosamine; Glycosaminoglycans; Heparin; Heparitin Sulfate; Monosaccharides; Quality Control
PubMed: 34626388
DOI: 10.1007/978-1-0716-1398-6_24 -
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 -
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 -
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 -
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 -
Advances in Neurobiology 2023Proteoglycans, and especially their GAG components, participate in numerous biologically significant interactions with growth factors, chemokines, morphogens, guidance... (Review)
Review
Proteoglycans, and especially their GAG components, participate in numerous biologically significant interactions with growth factors, chemokines, morphogens, guidance molecules, survival factors, and other extracellular and cell-surface components. These interactions are often critical to the basic developmental processes of cellular proliferation and differentiation, as well as to both the onset of disease sequelae and prevention of disease progression. In many tissues, proteoglycans and especially their glycosaminoglycan (GAG) components are mediators of these processes. The GAG family is characterized by covalently linked repeating disaccharides forming long unbranched polysaccharide chains. Thus far in higher eukaryotes, the family consists of chondroitin sulfate (CS), heparin/heparan sulfate (HS), dermatan sulfate (DS), keratan sulfate (KS) and hyaluronan (HA). All GAG chains (except HA) are characteristically modified by varying amounts of esterified sulfate. One or more GAG chains are usually found in nature bound to polypeptide backbones in the form of proteoglycans; HA is the exception. In the nervous system, GAG/proteoglycan-mediated interactions participate in proliferation and synaptogenesis, neural plasticity, and regeneration. This review focuses on the structure, chemistry and function of GAGs in nervous system development, disease, function and injury response.
Topics: Humans; Glycosaminoglycans; Chondroitin Sulfates; Dermatan Sulfate; Keratan Sulfate; Hyaluronic Acid; Heparitin Sulfate; Proteoglycans; Heparin; Disaccharides; Sulfates; Nervous System
PubMed: 36255674
DOI: 10.1007/978-3-031-12390-0_5 -
Frontiers in Cell and Developmental... 2022
PubMed: 35757004
DOI: 10.3389/fcell.2022.941178