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

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

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

Correspondence to: Bruce Caterson, Connective Tissue Biology Laboratory and Cardiff Institute of Tissue Engineering and Repair, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3US, Wales, United Kingdom. E-mail: Caterson{at}cardiff.ac.uk

Osteoarthritis is a chronic, debilitating joint disease characterized 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 recognizing novel chondroitin sulfate sulfation motif epitopes in glycosaminoglycans on proteoglycans can be used to identify metabolically distinct subpopulations of cells specifically within the superficial zone of the tissue and that flow cytometric analysis can recognize these cell subpopulations. Fluorochrome co-localization analysis suggests 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 microenvironment of superficial zone chondrocytes, seems 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 characterization 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. (J Histochem Cytochem 56:125–138, 2008)

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

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