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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 |
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creator | 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. |
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 > 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.</description><identifier>ISSN: 0730-2312</identifier><identifier>EISSN: 1097-4644</identifier><identifier>DOI: 10.1002/jcb.22108</identifier><identifier>PMID: 19259985</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>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</subject><ispartof>Journal of cellular biochemistry, 2009-05, Vol.107 (1), p.144-154</ispartof><rights>Copyright © 2009 Wiley‐Liss, Inc.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5178-3594eda53025ce41f0a950cc5f3007e0f8bf56d61c217708d51927e15da20ff03</citedby><cites>FETCH-LOGICAL-c5178-3594eda53025ce41f0a950cc5f3007e0f8bf56d61c217708d51927e15da20ff03</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19259985$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Teplyuk, Nadiya M.</creatorcontrib><creatorcontrib>Haupt, Larisa M.</creatorcontrib><creatorcontrib>Ling, Ling</creatorcontrib><creatorcontrib>Dombrowski, Christian</creatorcontrib><creatorcontrib>Mun, Foong Kin</creatorcontrib><creatorcontrib>Nathan, Saminathan S.</creatorcontrib><creatorcontrib>Lian, Jane B.</creatorcontrib><creatorcontrib>Stein, Janet L.</creatorcontrib><creatorcontrib>Stein, Gary S.</creatorcontrib><creatorcontrib>Cool, Simon M.</creatorcontrib><creatorcontrib>van Wijnen, Andre J.</creatorcontrib><title>The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts</title><title>Journal of cellular biochemistry</title><addtitle>J. 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 > 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.</description><subject>Animals</subject><subject>Blotting, Western</subject><subject>Cell Differentiation - physiology</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>Feedback, Physiological</subject><subject>fibroblast growth factor</subject><subject>Fibroblast Growth Factors - metabolism</subject><subject>Gene Expression Regulation</subject><subject>glycosaminoglycan</subject><subject>glypican</subject><subject>heparan sulfate</subject><subject>heparin</subject><subject>Mice</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>osteoblast</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - metabolism</subject><subject>Osteogenesis - physiology</subject><subject>proteoglycan</subject><subject>Proteoglycans - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Runx2</subject><subject>Signal Transduction - physiology</subject><subject>Stem Cells - cytology</subject><subject>Stem Cells - metabolism</subject><subject>syndecan</subject><issn>0730-2312</issn><issn>1097-4644</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2009</creationdate><recordtype>article</recordtype><recordid>eNp1kc1uEzEUhS0EomlhwQsgr5BYTHNtjzMzGySIIIDCj1ARS8vjsScuEzvYHpo8Qt8atxMKLFh54XO-e-49CD0hcE4A6PxSteeUEqjvoRmBpirKRVneRzOoGBSUEXqCTmO8BICmYfQhOiEN5U1T8xm6vtho7GPSvtfOKpyCdFEFu0vWO2ykSj7gL6PbUxx0Pw4y6YiV3-680y5F7A1OmWBsG3w7yJhwH_xV2hyt813wN-zhoKTD0fZODtb1WO5txNZNk2998RF6YOQQ9ePje4a-vnl9sXxbrD-t3i1frgvFSVUXjDel7iRnQLnSJTEgGw5KccMAKg2mbg1fdAuiKKkqqDuel6004Z2kYAywM_Ri4u7Gdqs7ldcIchC7YLcyHISXVvz74-xG9P6noA2pSygz4NkREPyPUccktjYqPQzSaT9GsahITsfrLHw-CVXwMQZt7oYQEDfFiVycuC0ua5_-neqP8thUFswnwZUd9OH_JPF--eo3spgcNh95f-eQ4XuOyCouvn1cCbaumyV8WInP7BdlGLYC</recordid><startdate>20090501</startdate><enddate>20090501</enddate><creator>Teplyuk, Nadiya M.</creator><creator>Haupt, Larisa M.</creator><creator>Ling, Ling</creator><creator>Dombrowski, Christian</creator><creator>Mun, Foong Kin</creator><creator>Nathan, Saminathan S.</creator><creator>Lian, Jane B.</creator><creator>Stein, Janet L.</creator><creator>Stein, Gary S.</creator><creator>Cool, Simon M.</creator><creator>van Wijnen, Andre J.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20090501</creationdate><title>The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts</title><author>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.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5178-3594eda53025ce41f0a950cc5f3007e0f8bf56d61c217708d51927e15da20ff03</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2009</creationdate><topic>Animals</topic><topic>Blotting, Western</topic><topic>Cell Differentiation - physiology</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>Feedback, Physiological</topic><topic>fibroblast growth factor</topic><topic>Fibroblast Growth Factors - metabolism</topic><topic>Gene Expression Regulation</topic><topic>glycosaminoglycan</topic><topic>glypican</topic><topic>heparan sulfate</topic><topic>heparin</topic><topic>Mice</topic><topic>Oligonucleotide Array Sequence Analysis</topic><topic>osteoblast</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - metabolism</topic><topic>Osteogenesis - physiology</topic><topic>proteoglycan</topic><topic>Proteoglycans - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Runx2</topic><topic>Signal Transduction - physiology</topic><topic>Stem Cells - cytology</topic><topic>Stem Cells - metabolism</topic><topic>syndecan</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Teplyuk, Nadiya M.</creatorcontrib><creatorcontrib>Haupt, Larisa M.</creatorcontrib><creatorcontrib>Ling, Ling</creatorcontrib><creatorcontrib>Dombrowski, Christian</creatorcontrib><creatorcontrib>Mun, Foong Kin</creatorcontrib><creatorcontrib>Nathan, Saminathan S.</creatorcontrib><creatorcontrib>Lian, Jane B.</creatorcontrib><creatorcontrib>Stein, Janet L.</creatorcontrib><creatorcontrib>Stein, Gary S.</creatorcontrib><creatorcontrib>Cool, Simon M.</creatorcontrib><creatorcontrib>van Wijnen, Andre J.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of cellular biochemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Teplyuk, Nadiya M.</au><au>Haupt, Larisa M.</au><au>Ling, Ling</au><au>Dombrowski, Christian</au><au>Mun, Foong Kin</au><au>Nathan, Saminathan S.</au><au>Lian, Jane B.</au><au>Stein, Janet L.</au><au>Stein, Gary S.</au><au>Cool, Simon M.</au><au>van Wijnen, Andre J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The osteogenic transcription factor Runx2 regulates components of the fibroblast growth factor/proteoglycan signaling axis in osteoblasts</atitle><jtitle>Journal of cellular biochemistry</jtitle><addtitle>J. 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 > 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.</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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