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JHC exPRESS: First Published October 15, 2007. doi:10.1369/jhc.7A7320.2007
Copyright © Histochemical Society, Inc.

A more recent version of this article appeared on February 1, 2008.
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Articles

Chondroitin Sulfate Sulfation Motifs as Putative Biomarkers for Isolation of Articular Cartilage Progenitor Cells

Anthony J. Hayes 1, Debbie Tudor 1, Mari A. Nowell 1, Bruce Caterson 1* and Clare E. Hughes 1

1 Connective Tissue Biology Laboratory and Cardiff Institute of Tissue Engineering and Repair, Cardiff School of Biosciences (AJH,DT,BC,CEH) and Medical Biochemistry and Immunology, Cardiff School of Medicine (MAN), Cardiff University, Cardiff, Wales, United Kingdom

* To whom correspondence should be addressed. E-mail: Caterson{at}cardiff.ac.uk.

Submitted on July 20, 2007
Accepted on 2 October 2007


  Abstract
Osteoarthritis is a chronic, debilitating joint disease characterised by progressive destruction of articular cartilage. Recently, a number of studies have identified a chondroprogenitor cell population within articular cartilage with significant potential for repair/regeneration. As yet there are few robust biomarkers of these cells. In this study we show that monoclonal antibodies recognising novel chondroitin sulfate sulfation motif epitopes in glycosaminoglycans on proteoglycans can be used to identify metabolically distinct sub-populations of cells specifically within the superficial zone of the tissue, and that flow cytometric analysis can recognize these cell sub-populations. Fluorochrome co-localisation analysis suggest that the chondroitin sulfate sulphation motifs are associated with a range of cell and extracellular matrix proteoglycans within the stem cell niche, that include perlecan and aggrecan, but not versican. The unique distributions of these sulphation motifs within the micro-environment of superficial zone chondrocytes appears to designate early stages of stem/progenitor cell differentiation and is consistent with these molecules playing a functional role in regulating aspects of chondrogenesis. The isolation and further characterisation of these cells will lead to an improved understanding of the role novel chondroitin sulfate sulfation plays in articular cartilage development and may contribute significantly to the field of articular cartilage repair.

Key Words: biomarker, chondroitin sulfate, sulfation motif epitopes, proteoglycans, chondroprogenitor, stem cell niche, immunohistochemistry, confocal microscopy, flow cytometry


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