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, Mun, Foong Kin, Nathan, Saminathan S., Lian, Jane B., Stein, Janet L., Stein, Gary S., Cool, Simon M., & van Wijnen, Andre 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), pp. 144-154.
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.
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|Item Type:||Journal Article|
|Additional Information:||Teplyuk, Nadiya M
Haupt, Larisa M
Mun, Foong Kin
Nathan, Saminathan S
Lian, Jane B
Stein, Janet L
Stein, Gary S
Cool, Simon M
van Wijnen, Andre J
R01 AR039588/AR/NIAMS NIH HHS/
R01 AR039588-18/AR/NIAMS NIH HHS/
R01 AR049069/AR/NIAMS NIH HHS/
R01 AR049069-06A2/AR/NIAMS NIH HHS/
R01 AR49069/AR/NIAMS NIH HHS/
Research Support, N.I.H., Extramural
J Cell Biochem. 2009 May 1;107(1):144-54. doi: 10.1002/jcb.22108.
|Keywords:||Animals, Blotting, Western, Cell Differentiation/physiology, Core Binding Factor Alpha 1 Subunit/*metabolism, Feedback, Physiological, Fibroblast Growth Factors/*metabolism, *Gene Expression Regulation, Mice, Oligonucleotide Array Sequence Analysis, Osteoblasts/cytology/*metabolism, Osteogenesis/*physiology, Proteoglycans/*metabolism, Reverse Transcriptase Polymerase Chain Reaction, Signal Transduction/physiology, Stem Cells/cytology/metabolism|
|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
|Deposited On:||02 Apr 2014 01:46|
|Last Modified:||02 Apr 2014 01:46|
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