The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts

Nadiya M. Teplyuk, Larisa M. Haupt, Ling Ling, Christian Dombrowski, Kin Mun Foong, Saminathan S. Nathan, Jane B. Lian, Janet L. Stein, Gary S. Stein, Simon M. Cool, Andre J van Wijnen

Research output: Contribution to journalArticle

57 Citations (Scopus)

Abstract

Heparan sulfate proteoglycans cooperate with basic fibroblast growth factor (bFGF/FGF2) signaling to control osteoblast growth and differentiation, as well as metabolic functions of osteoblasts. FGF2 signaling modulates the expression and activity of Runt-related transcription factor 2 (Runx2/Cbfa1), a key regulator of osteoblast proliferation and maturation. Here, we have characterized novel Runx2 target genes in osteoprogenitors under conditions that promote growth arrest while not yet permitting sustained phenotypic maturation. Runx2 enhances expression of genes related to proteoglycan-mediated signaling, including FGF receptors (e.g., FGFR2 and FGFR3) and proteoglycans (e.g., syndecans [Sdc1, Sdc2, Sdc3], glypicans [Gpc1], versican [Vcan]). Runx2 increases expression of the glycosyltransferase Exostosin-1 (Ext1) and heparanase, as well as alters the relative expression of N-linked sulfotransferases (Ndst1 = Ndst2 > Ndst3) and enzymes mediating O-linked sulfation of heparan sulfate (Hs2st > Hs6st) or chondroitin sulfate (Cs4st > Cs6st). Runx2 cooperates with FGF2 to induce expression of Sdc4 and the sulfatase Galns, but Runx2 and FGF2 suppress Gpc6, thus suggesting intricate Runx2 and FGF2 dependent changes in proteoglycan utilization. One functional consequence of Runx2 mediated modulations in proteoglycan-related gene expression is a change in the responsiveness of bone markers to FGF2 stimulation. Runx2 and FGF2 synergistically enhance osteopontin expression (> 100 fold), while FGF2 blocks Runx2 induction of alkaline phosphatase. Our data suggest that Runx2 and the FGF/proteoglycan axis may form an extracellular matrix (ECM)-related regulatory feed-back loop that controls osteoblast proliferation and execution of the osteogenic program.

Original languageEnglish (US)
Pages (from-to)144-154
Number of pages11
JournalJournal of Cellular Biochemistry
Volume107
Issue number1
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Fibroblast Growth Factors
Osteoblasts
Fibroblast Growth Factor 2
Proteoglycans
Transcription Factors
Syndecans
Genes
Glypicans
Versicans
Sulfatases
Gene Expression
Sulfotransferases
Fibroblast Growth Factor Receptors
Heparan Sulfate Proteoglycans
Glycosyltransferases
Osteopontin
Heparitin Sulfate
Chondroitin Sulfates
Growth
Gene expression

Keywords

  • Fibroblast growth factor
  • Glycosaminoglycan
  • Glypican
  • Heparan sulfate
  • Heparin
  • Osteoblast
  • Proteoglycan
  • Runx2
  • Syndecan

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Teplyuk, N. M., Haupt, L. M., Ling, L., Dombrowski, C., Foong, K. M., Nathan, S. S., ... van Wijnen, A. J. (2009). The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. Journal of Cellular Biochemistry, 107(1), 144-154. https://doi.org/10.1002/jcb.22108

The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. / Teplyuk, Nadiya M.; Haupt, Larisa M.; Ling, Ling; Dombrowski, Christian; Foong, Kin Mun; Nathan, Saminathan S.; Lian, Jane B.; Stein, Janet L.; Stein, Gary S.; Cool, Simon M.; van Wijnen, Andre J.

In: Journal of Cellular Biochemistry, Vol. 107, No. 1, 01.05.2009, p. 144-154.

Research output: Contribution to journalArticle

Teplyuk, NM, Haupt, LM, Ling, L, Dombrowski, C, Foong, KM, Nathan, SS, Lian, JB, Stein, JL, Stein, GS, Cool, SM & van Wijnen, AJ 2009, 'The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts', Journal of Cellular Biochemistry, vol. 107, no. 1, pp. 144-154. https://doi.org/10.1002/jcb.22108
Teplyuk, Nadiya M. ; Haupt, Larisa M. ; Ling, Ling ; Dombrowski, Christian ; Foong, Kin Mun ; Nathan, Saminathan S. ; Lian, Jane B. ; Stein, Janet L. ; Stein, Gary S. ; Cool, Simon M. ; van Wijnen, Andre J. / The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts. In: Journal of Cellular Biochemistry. 2009 ; Vol. 107, No. 1. pp. 144-154.
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AU - Dombrowski, Christian

AU - Foong, Kin Mun

AU - Nathan, Saminathan S.

AU - Lian, Jane B.

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