Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12
When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta 1 (TGF- beta 1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteobl...
Gespeichert in:
Veröffentlicht in: | Molecular and cellular biology 2000-12, Vol.20 (23), p.8783-8792 |
---|---|
Hauptverfasser: | , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 8792 |
---|---|
container_issue | 23 |
container_start_page | 8783 |
container_title | Molecular and cellular biology |
container_volume | 20 |
creator | Lee, K Kim, H Li, Q Chi, X Ueta, C Komori, T Wozney, J M Kim, E Choi, J Ryoo, H Bae, S |
description | When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta 1 (TGF- beta 1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF- beta 1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2 alpha A/Cbfa1, a global regulator of osteogenesis, as a major TGF- beta 1-responsive element binding protein induced by TGF- beta 1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF- beta 1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF- beta 1 and BMP-2 but not osteoblast-specific gene expression. Runx2 mimicked common effects of TGF- beta 1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF- beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells. |
doi_str_mv | 10.1128/MCB.20.23.8783-8792.2000 |
format | Article |
fullrecord | <record><control><sourceid>proquest</sourceid><recordid>TN_cdi_proquest_miscellaneous_17734006</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>17734006</sourcerecordid><originalsourceid>FETCH-LOGICAL-p116t-d45544b8d7c1997f4ced213736adde74b675c505a05247348dcb37660b6347fa3</originalsourceid><addsrcrecordid>eNotkctOwzAQRbMAifL4h1mxIsWPJE6XNIJSqRUIyho59qQNSuxgO6L8Mx-BS1mN5nHPvdIkCVAypZSVt-tqPmVkyvi0FCVPSzFjsSfkJJkQJkgqOCnOknPvP-KwmBE-SX5eRrNnsPQgobJ9bw1spNtiANvAxknjG-v61mxh4exX2MGDVME6qDFIoCCNhrk1CGvrhp3dosHQKnh2NmBrgN38XVTWDuhkaCM9Cr8QDRx9D9vXXuoclkaPCj08-YC27qQP6euAqm0ibhGxcL8fHHp_YERy2CE8d6Nrh-hkAqzRo1G771520R3V6HxMWWHXwaqN6opVlF0mp43sPF7914vk7eF-Uz2mq6fFsrpbpQOlRUh1ludZVpdaKDqbiSZTqBnlghdSaxRZXYhc5SSXJGeZ4FmpVc1FUZC64JloJL9Iro_cwdnPEX1471uvYhZp0I7-nYqoih_gvwa4iMw</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17734006</pqid></control><display><type>article</type><title>Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12</title><source>PubMed Central Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Lee, K ; Kim, H ; Li, Q ; Chi, X ; Ueta, C ; Komori, T ; Wozney, J M ; Kim, E ; Choi, J ; Ryoo, H ; Bae, S</creator><creatorcontrib>Lee, K ; Kim, H ; Li, Q ; Chi, X ; Ueta, C ; Komori, T ; Wozney, J M ; Kim, E ; Choi, J ; Ryoo, H ; Bae, S</creatorcontrib><description>When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta 1 (TGF- beta 1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF- beta 1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2 alpha A/Cbfa1, a global regulator of osteogenesis, as a major TGF- beta 1-responsive element binding protein induced by TGF- beta 1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF- beta 1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF- beta 1 and BMP-2 but not osteoblast-specific gene expression. Runx2 mimicked common effects of TGF- beta 1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF- beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.</description><identifier>ISSN: 0270-7306</identifier><identifier>DOI: 10.1128/MCB.20.23.8783-8792.2000</identifier><language>eng</language><subject>Cbfa1 protein ; PEBP2 protein ; Runx2 protein ; Smad5 protein</subject><ispartof>Molecular and cellular biology, 2000-12, Vol.20 (23), p.8783-8792</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids></links><search><creatorcontrib>Lee, K</creatorcontrib><creatorcontrib>Kim, H</creatorcontrib><creatorcontrib>Li, Q</creatorcontrib><creatorcontrib>Chi, X</creatorcontrib><creatorcontrib>Ueta, C</creatorcontrib><creatorcontrib>Komori, T</creatorcontrib><creatorcontrib>Wozney, J M</creatorcontrib><creatorcontrib>Kim, E</creatorcontrib><creatorcontrib>Choi, J</creatorcontrib><creatorcontrib>Ryoo, H</creatorcontrib><creatorcontrib>Bae, S</creatorcontrib><title>Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12</title><title>Molecular and cellular biology</title><description>When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta 1 (TGF- beta 1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF- beta 1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2 alpha A/Cbfa1, a global regulator of osteogenesis, as a major TGF- beta 1-responsive element binding protein induced by TGF- beta 1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF- beta 1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF- beta 1 and BMP-2 but not osteoblast-specific gene expression. Runx2 mimicked common effects of TGF- beta 1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF- beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.</description><subject>Cbfa1 protein</subject><subject>PEBP2 protein</subject><subject>Runx2 protein</subject><subject>Smad5 protein</subject><issn>0270-7306</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2000</creationdate><recordtype>article</recordtype><recordid>eNotkctOwzAQRbMAifL4h1mxIsWPJE6XNIJSqRUIyho59qQNSuxgO6L8Mx-BS1mN5nHPvdIkCVAypZSVt-tqPmVkyvi0FCVPSzFjsSfkJJkQJkgqOCnOknPvP-KwmBE-SX5eRrNnsPQgobJ9bw1spNtiANvAxknjG-v61mxh4exX2MGDVME6qDFIoCCNhrk1CGvrhp3dosHQKnh2NmBrgN38XVTWDuhkaCM9Cr8QDRx9D9vXXuoclkaPCj08-YC27qQP6euAqm0ibhGxcL8fHHp_YERy2CE8d6Nrh-hkAqzRo1G771520R3V6HxMWWHXwaqN6opVlF0mp43sPF7914vk7eF-Uz2mq6fFsrpbpQOlRUh1ludZVpdaKDqbiSZTqBnlghdSaxRZXYhc5SSXJGeZ4FmpVc1FUZC64JloJL9Iro_cwdnPEX1471uvYhZp0I7-nYqoih_gvwa4iMw</recordid><startdate>20001201</startdate><enddate>20001201</enddate><creator>Lee, K</creator><creator>Kim, H</creator><creator>Li, Q</creator><creator>Chi, X</creator><creator>Ueta, C</creator><creator>Komori, T</creator><creator>Wozney, J M</creator><creator>Kim, E</creator><creator>Choi, J</creator><creator>Ryoo, H</creator><creator>Bae, S</creator><scope>7QP</scope><scope>7TM</scope></search><sort><creationdate>20001201</creationdate><title>Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12</title><author>Lee, K ; Kim, H ; Li, Q ; Chi, X ; Ueta, C ; Komori, T ; Wozney, J M ; Kim, E ; Choi, J ; Ryoo, H ; Bae, S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p116t-d45544b8d7c1997f4ced213736adde74b675c505a05247348dcb37660b6347fa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2000</creationdate><topic>Cbfa1 protein</topic><topic>PEBP2 protein</topic><topic>Runx2 protein</topic><topic>Smad5 protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lee, K</creatorcontrib><creatorcontrib>Kim, H</creatorcontrib><creatorcontrib>Li, Q</creatorcontrib><creatorcontrib>Chi, X</creatorcontrib><creatorcontrib>Ueta, C</creatorcontrib><creatorcontrib>Komori, T</creatorcontrib><creatorcontrib>Wozney, J M</creatorcontrib><creatorcontrib>Kim, E</creatorcontrib><creatorcontrib>Choi, J</creatorcontrib><creatorcontrib>Ryoo, H</creatorcontrib><creatorcontrib>Bae, S</creatorcontrib><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Nucleic Acids Abstracts</collection><jtitle>Molecular and cellular biology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lee, K</au><au>Kim, H</au><au>Li, Q</au><au>Chi, X</au><au>Ueta, C</au><au>Komori, T</au><au>Wozney, J M</au><au>Kim, E</au><au>Choi, J</au><au>Ryoo, H</au><au>Bae, S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12</atitle><jtitle>Molecular and cellular biology</jtitle><date>2000-12-01</date><risdate>2000</risdate><volume>20</volume><issue>23</issue><spage>8783</spage><epage>8792</epage><pages>8783-8792</pages><issn>0270-7306</issn><abstract>When C2C12 pluripotent mesenchymal precursor cells are treated with transforming growth factor beta 1 (TGF- beta 1), terminal differentiation into myotubes is blocked. Treatment with bone morphogenetic protein 2 (BMP-2) not only blocks myogenic differentiation of C2C12 cells but also induces osteoblast differentiation. The molecular mechanisms governing the ability of TGF- beta 1 and BMP-2 to both induce ligand-specific responses and inhibit myogenic differentiation are not known. We identified Runx2/PEBP2 alpha A/Cbfa1, a global regulator of osteogenesis, as a major TGF- beta 1-responsive element binding protein induced by TGF- beta 1 and BMP-2 in C2C12 cells. Consistent with the observation that Runx2 can be induced by either TGF- beta 1 or BMP-2, the exogenous expression of Runx2 mediated some of the effects of TGF- beta 1 and BMP-2 but not osteoblast-specific gene expression. Runx2 mimicked common effects of TGF- beta 1 and BMP-2 by inducing expression of matrix gene products (for example, collagen and fibronectin), suppressing MyoD expression, and inhibiting myotube formation of C2C12 cells. For osteoblast differentiation, an additional effector, BMP-specific Smad protein, was required. Our results indicate that Runx2 is a major target gene shared by TGF- beta and BMP signaling pathways and that the coordinated action of Runx2 and BMP-activated Smads leads to the induction of osteoblast-specific gene expression in C2C12 cells.</abstract><doi>10.1128/MCB.20.23.8783-8792.2000</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0270-7306 |
ispartof | Molecular and cellular biology, 2000-12, Vol.20 (23), p.8783-8792 |
issn | 0270-7306 |
language | eng |
recordid | cdi_proquest_miscellaneous_17734006 |
source | PubMed Central Free; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Cbfa1 protein PEBP2 protein Runx2 protein Smad5 protein |
title | Runx2 Is a Common Target of Transforming Growth Factor beta 1 and Bone Morphogenetic Protein 2, and Cooperation between Runx2 and Smad5 Induces Osteoblast-Specific Gene Expression in the Pluripotent Mesenchymal Precursor Cell Line C2C12 |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T13%3A18%3A52IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Runx2%20Is%20a%20Common%20Target%20of%20Transforming%20Growth%20Factor%20beta%201%20and%20Bone%20Morphogenetic%20Protein%202,%20and%20Cooperation%20between%20Runx2%20and%20Smad5%20Induces%20Osteoblast-Specific%20Gene%20Expression%20in%20the%20Pluripotent%20Mesenchymal%20Precursor%20Cell%20Line%20C2C12&rft.jtitle=Molecular%20and%20cellular%20biology&rft.au=Lee,%20K&rft.date=2000-12-01&rft.volume=20&rft.issue=23&rft.spage=8783&rft.epage=8792&rft.pages=8783-8792&rft.issn=0270-7306&rft_id=info:doi/10.1128/MCB.20.23.8783-8792.2000&rft_dat=%3Cproquest%3E17734006%3C/proquest%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17734006&rft_id=info:pmid/&rfr_iscdi=true |