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

Larisa M. Haupt, Sadasivam Murali, Kin Mun Foong, Nadiya Teplyuk, Fong Mei Leong, Gary S. Stein, Andre J van Wijnen, Victor Nurcombe, Simon M. Cool

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)780-791
Number of pages12
JournalJournal of Cellular Physiology
Volume220
Issue number3
DOIs
StatePublished - Sep 2009
Externally publishedYes

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Glypicans
Heparan Sulfate Proteoglycans
Heparitin Sulfate
Osteogenesis
Fibroblast Growth Factor Receptors
Gene expression
Extracellular Matrix
Versicans
Biglycan
Decorin
Gene Knockdown Techniques
Chondroitin Sulfate Proteoglycans
Null Lymphocytes
Fibroblast Growth Factor 2
Proteoglycans
Transcriptome
Sugars
Small Interfering RNA
Culture Media
Intercellular Signaling Peptides and Proteins

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Haupt, L. M., Murali, S., Foong, K. M., Teplyuk, N., Leong, F. M., Stein, G. S., ... 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), 780-791. https://doi.org/10.1002/jcp.21825

The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis. / Haupt, Larisa M.; Murali, Sadasivam; Foong, Kin Mun; Teplyuk, Nadiya; Leong, Fong Mei; Stein, Gary S.; van Wijnen, Andre J; Nurcombe, Victor; Cool, Simon M.

In: Journal of Cellular Physiology, Vol. 220, No. 3, 09.2009, p. 780-791.

Research output: Contribution to journalArticle

Haupt, LM, Murali, S, Foong, KM, Teplyuk, N, Leong, FM, Stein, GS, van Wijnen, AJ, Nurcombe, V & Cool, SM 2009, 'The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis', Journal of Cellular Physiology, vol. 220, no. 3, pp. 780-791. https://doi.org/10.1002/jcp.21825
Haupt, Larisa M. ; Murali, Sadasivam ; Foong, Kin Mun ; Teplyuk, Nadiya ; Leong, Fong Mei ; Stein, Gary S. ; van Wijnen, Andre J ; Nurcombe, Victor ; Cool, Simon M. / The heparan sulfate proteoglycan (HSPG) glypican-3 mediates commitment of MC3T3-E1 cells toward osteogenesis. In: Journal of Cellular Physiology. 2009 ; Vol. 220, No. 3. pp. 780-791.
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