Concise Review: Stem/Progenitor Cell Proteoglycans Decorated with 7-D-4, 4-C-3, and 3-B-3(-) Chondroitin Sulfate Motifs Are Morphogenetic Markers of Tissue Development

Abstract

This study reviewed the occurrence of chondroitin sulfate (CS) motifs 4-C-3, 7-D-4, and 3-B-3(-), which are expressed by progenitor cells in tissues undergoing morphogenesis. These motifs have a transient early expression pattern during tissue development and also appear in mature tissues during pathological remodeling and attempted repair processes by activated adult stem cells. The CS motifs are information and recognition modules, which may regulate cellular behavior and delineate stem cell niches in developmental tissues. One of the difficulties in determining the precise role of stem cells in tissue development and repair processes is their short engraftment period and the lack of specific markers, which differentiate the activated stem cell lineages from the resident cells. The CS sulfation motifs 7-D-4, 4-C-3, and 3-B-3 (-) decorate cell surface proteoglycans on activated stem/progenitor cells and appear to identify these cells in transitional areas of tissue development and in tissue repair and may be applicable to determining a more precise role for stem cells in tissue morphogenesis. Stem Cells 2018;36:1475-1486.

Electro‐Stimulation, a Promising Therapeutic Treatment Modality for Tissue Repair: Emerging Roles of Sulfated Glycosaminoglycans as Electro‐Regulatory Mediators of Intrinsic Repair Processes

“…Significantly the 3‐B‐3(‐) and 7‐D‐4 CS sulfation motifs are also expressed by such cell clusters in inner AF regions undergoing reparative changes, [ 16 ] this is consistent with the synthesis of these CS sulfation motifs by stem cell populations [ 17 ] and the cell directive properties proposed for these CS glyco‐forms. [ 18 ] Administered stem cells exhibit a strong reparative response in experimental disc degeneration, producing a 95% recovery in disc height and recovery of a normal tissue composition and biomechanical material properties.…”

“…[ 17 ] These motifs have specific localization patterns in tissue morphogenesis consistent with the roles of chondroprogenitor cells in early tissue development. [ 18,34 ] The current understanding is that these CS sulfation motifs have specific cell directive properties in transitional tissues in development and in tissue repair [ 17,18 ] which however, await full characterization. [ 13 ]…”

Glycosaminoglycan and Proteoglycan Biotherapeutics in Articular Cartilage Protection and Repair Strategies: Novel Approaches to Visco‐supplementation in Orthobiologics

“…[36] GAG evolution over 500 million years of vertebrate and invertebrate evolution [37] has selected for GAGs equipped with molecular recognition and information transfer properties. [13,14,[39][40][41][42][43][44] [38][39][40] Thus GAGs and PGs evolved which have regulatory properties over downstream cell-signaling pathways and gene expression networks essential for physiological life processes.…”

“…Attempts are being made to better understand the glycocode of GAGs in order to better determine their specific contributions in tissue development and ECM remodeling since this information may be of potential application in repair biology. [13,14,[39][40][41][42][43][44]…”

Osteoarthritis as an organ disease: from the cradle to the grave

“…Work from Bruce Caterson's lab shows that there are specific epitopes of chondroitin sulphate (4-C-3, 7-D-4 and 3-B-3(-)), more commonly found in foetal tissue, decorating the cell surface proteoglycans on activated stem cells. This could be a signal that these cells are a target for tissue development (Hayes et al, 2018). The significance of these specific epitopes is that they are commonly found on progenitor cells, which occur in increased numbers in OA tissue.…”