Roles of Chondroitin Sulfate Proteoglycans as Regulators of Skeletal Development

Abstract

The extracellular matrix (ECM) is critically important for most cellular processes including differentiation, morphogenesis, growth, survival and regeneration. The interplay between cells and the ECM often involves bidirectional signaling between ECM components and small molecules, i.e., growth factors, morphogens, hormones, etc., that regulate critical life processes. The ECM provides biochemical and contextual information by binding, storing, and releasing the bioactive signaling molecules, and/or mechanical information that signals from the cell membrane integrins through the cytoskeleton to the nucleus, thereby influencing cell phenotypes. Using these dynamic, reciprocal processes, cells can also remodel and reshape the ECM by degrading and re-assembling it, thereby sculpting their environments. In this review, we summarize the role of chondroitin sulfate proteoglycans as regulators of cell and tissue development using the skeletal growth plate model, with an emphasis on use of naturally occurring, or created mutants to decipher the role of proteoglycan components in signaling paradigms.

Adaptable synthesis of chondroitin sulfate disaccharide subtypes preprogrammed for regiospecific O-sulfation

“…2 Naturally occurring CS therefore contains an assortment of subtypes, and CS interacts with growth factors, cytokines, chemokines and adhesion molecules, 6 regulating physiological processes including embryonic and brain development, 7,8 anti-inflammatory effects, 9 wound healing 10 and signalling. 11 Whilst it is established that CS sulfation patterns correlate to related biological function, the specificities of such molecular interactions is an underdeveloped field. 12 Access to homogenous, structurally defined CS oligosaccharides is therefore of utmost importance for the study of related CS-protein interactions, but is hampered by difficulties in obtaining significant amounts of structurally defined sequences from natural sources, particularly for rarer subtypes such as CS-D. Relatedly, synthetic approaches to heparan sulfate (HS) fragments have advanced more rapidly and proven extremely successful.…”