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Glycosaminoglycan composition changes with MG‐63 osteosarcoma osteogenesis in vitro and induces human mesenchymal stem cell aggregation
Author(s) -
Kumarasuriyar A.,
Murali S.,
Nurcombe V.,
Cool S.M.
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21620
Subject(s) - mesenchymal stem cell , glycosaminoglycan , extracellular matrix , microbiology and biotechnology , proteoglycan , osteosarcoma , chemistry , stem cell , cellular differentiation , osteoblast , cell growth , cell culture , cell , in vitro , biology , biochemistry , cancer research , genetics , gene
Osteogenic differentiation is coordinated by the exposure of cells to temporal changes in a combination of growth factors and elements within the extracellular matrix (ECM). Many of the key proteins that drive these changes share the property of being dependent on ECM glycosaminoglycans (GAGs) for their activity. Here, we examined whether GAGs isolated from proliferating, differentiating and mineralizing MG‐63 osteosarcoma cells differed in their physical properties, and thus in their capacities to coordinate the osteogenic cascade both in human MG‐63 osteosarcoma cells and primary human mesenchymal stem cells (hMSCs). Our results show that the size distribution of GAGs, the expression of GAG‐carrying proteoglycan cores and the expression of enzymes involved in their modification systematically change as MG‐63 cells mature in culture. When dosed back onto cells exogenously in soluble form, GAGs regulated MG‐63 survival and growth in a dose‐dependent manner, but not differentiation in either cell type. In contrast, hMSCs aggregated into distinct colonies when grown on GAG‐coated substrates, while MG‐63 cells did not. Heparin‐coated substrates improved hMSC viability without inducing aggregation. These results suggest a complex role for GAGs in coordinating the emergence of the osteoblast phenotype, and provide further evidence for the use of heparans in bone tissue repair applications. J. Cell. Physiol. 218: 501–511, 2009. © 2008 Wiley‐Liss, Inc.