The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis

Haupt, Larisa M., Murali, S., Mun, F. K., Teplyuk, N., Mei, L. F., Stein, G. S., van Wijnen, A. J., Nurcombe, V., & Cool, S. M. (2009) The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis. Journal of Cellular Physiology, 220(3), pp. 780-791.

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Abstract

Heparan sulfate (HS) sugar chains attached to core proteoglycans (PGs) termed HSPGs mediate an extensive range of cell-extracellular matrix (ECM) and growth factor interactions based upon their sulfation patterns. When compared with non-osteogenic (maintenance media) culture conditions, under established osteogenic culture conditions, MC3T3-E1 cells characteristically increase their osteogenic gene expression profile and switch their dominant fibroblast growth factor receptor (FGFR) from FGFR1 (0.5-fold decrease) to FGFR3 (1.5-fold increase). The change in FGFR expression profile of the osteogenic-committed cultures was reflected by their inability to sustain an FGF-2 stimulus, but respond to BMP-2 at day 14 of culture. The osteogenic cultures decreased their chondroitin and dermatan sulfate PGs (biglycan, decorin, and versican), but increased levels of the HS core protein gene expression, in particular glypican-3. Commitment and progress through osteogenesis is accompanied by changes in FGFR expression, decreased GAG initiation but increased N- and O-sulfation and reduced remodeling of the ECM (decreased heparanase expression) resulting in the production of homogenous (21 kDa) HS chain. With the HSPG glypican-3 expression strongly upregulated in these processes, siRNA was used to knockdown this gene to examine the effect on osteogenic commitment. Reduced glypican-3 abrogated the expression of Runx2, and thus differentiation. The reintroduction of this HSPG into Runx2-null cells allowed osteogenesis to proceed. These results demonstrate the dependence of osteogenesis on specific HS chains, in particular those associated with glypican-3.

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ID Code: 69469
Item Type: Journal Article
Refereed: Yes
Additional Information: Haupt, Larisa M
Murali, Sadasivam
Mun, Foong Kin
Teplyuk, Nadiya
Mei, Leong Fong
Stein, Gary S
van Wijnen, Andre J
Nurcombe, Victor
Cool, Simon M
eng
Research Support, Non-U.S. Gov't
2009/05/30 09:00
J Cell Physiol. 2009 Sep;220(3):780-91. doi: 10.1002/jcp.21825.
Additional URLs:
Keywords: 3T3 Cells, Animals, Biglycan, Bone Morphogenetic Protein 2/metabolism, *Cell Differentiation/genetics, *Cell Lineage/genetics, Cell Proliferation, Core Binding Factor Alpha 1 Subunit/genetics/metabolism, Decorin, Extracellular Matrix Proteins/metabolism, Fibroblast Growth Factor 2/metabolism, Gene Expression Regulation, Enzymologic, Glypicans/genetics/*metabolism, Heparin Lyase/genetics/metabolism, Humans, Mice, Mice, Knockout, Osteoblasts/enzymology/*metabolism, *Osteogenesis/genetics, *Protein Processing, Post-Translational, Proteoglycans/metabolism, RNA Interference, RNA, Messenger/metabolism, Receptors, Fibroblast Growth Factor/metabolism, Recombinant Proteins/metabolism, Sulfotransferases/genetics/metabolism, Time Factors, Transfection, Versicans/metabolism
DOI: 10.1002/jcp.21825
ISSN: 1097-4652 (Electronic)0021-9541 (Linking)
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > BIOCHEMISTRY AND CELL BIOLOGY (060100) > Cell Development Proliferation and Death (060103)
Divisions: Current > Schools > School of Biomedical Sciences
Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Copyright Owner: Copyright 2009 Wiley-Liss, Inc.
Copyright Statement: Author's Pre-print: author can archive pre-print (ie pre-refereeing)
Author's Post-print: subject to Restrictions below, author can archive post-print (ie final draft post-refereeing)
Restrictions: •12 months embargo for scientific, technical or medical journals
•2 years embargo for social sciences and humanities journals

Publisher's Version/PDF: author cannot archive publisher's version/PDF
Deposited On: 06 Apr 2014 23:31
Last Modified: 29 May 2014 03:32

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