Roles of Chondroitin Sulfate and Dermatan Sulfate as Regulators for Cell and Tissue Development

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About this Research Topic

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Background

Chondroitin sulfate (CS) and dermatan sulfate (DS) are key glycosaminoglycans (GAGs)
regulating various biological events, such as assembly of the extracellular matrix, tissue
development and regeneration, and cell signaling elicited by interactions with extracellular matrix
components, morphogens, and growth factors. CS and DS, which are integral glycan structures
of numerous proteoglycans (PGs), are widely distributed throughout the extracellular matrix as
well as on the cell surface. The diverse functions of both CS and DS are governed by their
sulfation patterns, which determine their specific binding properties. Accordingly, CS-A, CS-C,
CS-D, CS-E, and DS, which are modified by sulfation at different position of hydroxyl group of
the sugar moiety, are, for instance, involved in bacterial infection, bone and neuronal development,
tumor growth and metastasis, and organization of the tissue architecture in different organs.

Recent functional studies on CS and DS demonstrated their indispensable roles in various
biological and pathological contexts including neuronal and stem cell behavior, brain, bone and
skin development and cancer progression, and have further been associated with a variety of
human genetic disorders. For instance, heart defects and neurological abnormalities, in addition
to connective tissue diseases such as spondyloepiphyseal dysplasia and Ehlers-Danlos syndrome,
have been reported to be caused by mutations in the genes encoding glycosyltransferases,
epimerases, and sulfotransferases that are responsible for the biosynthesis of CS and DS. These
observations suggest that CS and DS are potential targets of drugs for human diseases.

Nevertheless, the pathological and molecular mechanisms underlying the precise functions of
CS and DS in these different contexts remain to be fully elucidated. Still not fully resolved issues
include the precise relationship between PG core protein and CS/DS variant in the exertion of
different functions, which cell signaling pathways are directly regulated by the GAGs, which are
their binding partners, and how tertiary structures created by CS/DS binding to these molecules
are critically involved the control of biological and pathological events.

Chondroitin sulfate (CS) and dermatan sulfate (DS) are key molecules that regulate various
biological events such as construction of the extracellular matrix, tissue development, and cell
signaling through interactions with extracellular matrix components, morphogens, and growth
factors. CS and DS, which are side chains of proteoglycans (PGs), are distributed in extracellular
matrix as well as at cell surface. The diverse functions of both CS and DS are governed by their
sulfation modification, which gives a rise to the specific binding proteins. Recent functional
studies on CS and DS demonstrated its indispensable roles in various biological events including
neuronal and stem cell behaviors, brain, bone, skin developments, cancer development as well as
metastasis, and human genetic disorders.

Recent functional studies on CS and DS demonstrated its indispensable roles in various
biological events including neuronal and stem cell behaviors, brain, bone, skin developments,
cancer development as well as metastasis, and human genetic disorders. However, the
pathological and molecular mechanisms for functions of CS and DS remains to be elucidated. For
example, which core proteins of PGs, cell signaling pathways, binding molecules, how tertiary
structures of CS/DS with binding proteins are critical in these mechanisms. Thus, we wish to
achieve two goals: 1) to identify core protein(s), signal pathway(s), interacting protein(s), tertiary
structure(s) involved in the CS and DS in cell differentiation, tissue development, and human
diseases; 2) to provide the insight into new drugs, medicines, and diagnosis for human diseases
caused by metabolic abnormality of CS and DS.

The following areas can be covered in the scope of this Research Topic:
•Cell signaling of CS/DS
•Stem cells, iPS cells, and regenerative models
•Development of model animals in CS/DS
•Interactions of CS/DS with various proteins
•Neuronal development of CS/DS
•Metabolism of CS/DS
•Chemical biology of CS/DS
•Human genetic diseases in CS/DS
•Tumor biology of CS/DS
•Pathobiochemistry of CS/DS
•CS/DS oligosaccharide
•CS/DS as drugs

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