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

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)...

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Published in:Journal of cellular biochemistry 2009-05, Vol.107 (1), p.144-154
Main Authors: 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.
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cited_by cdi_FETCH-LOGICAL-c5178-3594eda53025ce41f0a950cc5f3007e0f8bf56d61c217708d51927e15da20ff03
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container_title Journal of cellular biochemistry
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creator Teplyuk, Nadiya M.
Haupt, Larisa M.
Ling, Ling
Dombrowski, Christian
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Stein, Gary S.
Cool, Simon M.
van Wijnen, Andre J.
description 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. J. Cell. Biochem. 107: 144–154, 2009. © 2009 Wiley‐Liss, Inc.
doi_str_mv 10.1002/jcb.22108
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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 &gt; Ndst3) and enzymes mediating O‐linked sulfation of heparan sulfate (Hs2st &gt; Hs6st) or chondroitin sulfate (Cs4st &gt; 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 (&gt;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. J. Cell. 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Cell. Biochem</addtitle><description>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 &gt; Ndst3) and enzymes mediating O‐linked sulfation of heparan sulfate (Hs2st &gt; Hs6st) or chondroitin sulfate (Cs4st &gt; 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 (&gt;100 fold), while FGF2 blocks Runx2 induction of alkaline phosphatase. 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Cell. Biochem</addtitle><date>2009-05-01</date><risdate>2009</risdate><volume>107</volume><issue>1</issue><spage>144</spage><epage>154</epage><pages>144-154</pages><issn>0730-2312</issn><eissn>1097-4644</eissn><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 &gt; Ndst3) and enzymes mediating O‐linked sulfation of heparan sulfate (Hs2st &gt; Hs6st) or chondroitin sulfate (Cs4st &gt; 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 (&gt;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. J. Cell. Biochem. 107: 144–154, 2009. © 2009 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>19259985</pmid><doi>10.1002/jcb.22108</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Blotting, Western
Cell Differentiation - physiology
Core Binding Factor Alpha 1 Subunit - metabolism
Feedback, Physiological
fibroblast growth factor
Fibroblast Growth Factors - metabolism
Gene Expression Regulation
glycosaminoglycan
glypican
heparan sulfate
heparin
Mice
Oligonucleotide Array Sequence Analysis
osteoblast
Osteoblasts - cytology
Osteoblasts - metabolism
Osteogenesis - physiology
proteoglycan
Proteoglycans - metabolism
Reverse Transcriptase Polymerase Chain Reaction
Runx2
Signal Transduction - physiology
Stem Cells - cytology
Stem Cells - metabolism
syndecan
title The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts
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