Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells


Autoria(s): Dombrowski, Christian; Song, Shu Jun; Chuan, Peiying; Lim, Xinhong; Susanto, Evelyn; Sawyer, Amber A.; Woodruff, Maria A.; Hutmacher, Dietmar W.; Nurcombe, Victor; Cool, Simon M.
Data(s)

08/08/2009

Resumo

The growth and differentiation of mesenchymal stem cells is controlled by various growth factors, the activities of which can be modulated by heparan sulfates. We have previously underscored the necessity of sulfated glycosaminoglycans for the FGF-2-stimulated differentiation of osteoprogenitor cells. Here we show that exogenous application of heparan sulfate to cultures of primary rat MSCs stimulates their proliferation leading to increased expression of osteogenic markers and enhanced bone nodule formation. FGF-2 can also increase the proliferation and osteogenic differentiation of rMSCs when applied exogenously during their linear growth. However, as opposed to exogenous HS, the continuous use of FGF-2 during in vitro differentiation completely blocked rMSC mineralization. Furthermore, we show that the effects of both FGF-2 and HS are mediated through FGF receptor 1 (FGFR1) and that inhibition of signaling through this receptor arrests cell growth resulting in the cells being unable to reach the critical density necessary to induce differentiation. Interestingly, blocking FGFR1 signaling in post-confluent osteogenic cultures significantly increased calcium deposition. Taken together our data clearly suggests that FGFR1 signaling plays an important role during osteogenic differentiation, firstly by stimulating cell growth that is closely followed by an inhibitory affect once the cells have reached confluence. It also underlines the importance of HS as a co-receptor for the signaling of endogenous FGF-2 and suggests that purified glycosaminoglycans may be attractive alternatives to growth factors for improved ex vivo growth and differentiation of MSCs.

Formato

application/pdf

Identificador

http://eprints.qut.edu.au/31246/

Publicador

Mary Ann Liebert Inc

Relação

http://eprints.qut.edu.au/31246/1/heparan_sulfat_mediates_the_proliferation_and_differentiation_of_rat.pdf

DOI:10.1089/scd.2008.0157

Dombrowski, Christian, Song, Shu Jun, Chuan, Peiying, Lim, Xinhong, Susanto, Evelyn, Sawyer, Amber A., Woodruff, Maria A., Hutmacher, Dietmar W., Nurcombe, Victor, & Cool, Simon M. (2009) Heparan sulfate mediates the proliferation and differentiation of rat mesenchymal stem cells. Stem Cells and Development, 18(4), pp. 661-670.

Direitos

Copyright 2009 Mary Ann Liebert Inc.

Fonte

Faculty of Built Environment and Engineering; Institute of Health and Biomedical Innovation; School of Engineering Systems

Palavras-Chave #060103 Cell Development Proliferation and Death #mesenchymal stem cells
Tipo

Journal Article