Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis
Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we...
Gespeichert in:
| Veröffentlicht in: | Cell 2004-11, Vol.119 (4), p.555-566 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 566 |
|---|---|
| container_issue | 4 |
| container_start_page | 555 |
| container_title | Cell |
| container_volume | 119 |
| creator | Vega, Rick B. Matsuda, Koichi Oh, Junyoung Barbosa, Ana C. Yang, Xiangli Meadows, Eric McAnally, John Pomajzl, Chris Shelton, John M. Richardson, James A. Karsenty, Gerard Olson, Eric N. |
| description | Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy. HDAC4-null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy, mimicking the phenotype that results from constitutive Runx2 expression in chondrocytes. Conversely, overexpression of HDAC4 in proliferating chondrocytes in vivo inhibits chondrocyte hypertrophy and differentiation, mimicking a Runx2 loss-of-function phenotype. These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy. |
| doi_str_mv | 10.1016/j.cell.2004.10.024 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_67064872</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S0092867404010347</els_id><sourcerecordid>67064872</sourcerecordid><originalsourceid>FETCH-LOGICAL-c493t-d5ae0c4be45b18e4e2629a21b63ce168a17675194633490721369c76779f3d1c3</originalsourceid><addsrcrecordid>eNqFkDtPwzAYRS0EglL4AwwoE1uC7fgRSywoPIpUiQGYrcT52rqkcbATpPx7ErUSG0xXujr3DgehK4ITgom43SYG6jqhGLOxSDBlR2hGsJIxI5IeoxnGisaZkOwMnYewxRhnnPNTdEY4TyVnbIaWCxs610D0AIWBbqiLABGLctd03tUhyjeuqbwzQwfRYmjBj3W7GaKq97ZZR2-fUEPn1tBAsOECnayKOsDlIefo4-nxPV_Ey9fnl_x-GRum0i6ueAHYsBIYL0kGDKigqqCkFKkBIrKCSCE5UUykKVNYUpIKZcZOqlVaEZPO0c3-t_Xuq4fQ6Z0Nk4uiAdcHLSQWLJP0X5BIKUSmyAjSPWi8C8HDSrfe7go_aIL1JFtv9bTTk-ypG2WPo-vDe1_uoPqdHOyOwN0egFHGtwWvg7HQGKisB9Ppytm__n8AT5KPkA</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>17766891</pqid></control><display><type>article</type><title>Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis</title><source>MEDLINE</source><source>Cell Press Free Archives</source><source>Elsevier ScienceDirect Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><creator>Vega, Rick B. ; Matsuda, Koichi ; Oh, Junyoung ; Barbosa, Ana C. ; Yang, Xiangli ; Meadows, Eric ; McAnally, John ; Pomajzl, Chris ; Shelton, John M. ; Richardson, James A. ; Karsenty, Gerard ; Olson, Eric N.</creator><creatorcontrib>Vega, Rick B. ; Matsuda, Koichi ; Oh, Junyoung ; Barbosa, Ana C. ; Yang, Xiangli ; Meadows, Eric ; McAnally, John ; Pomajzl, Chris ; Shelton, John M. ; Richardson, James A. ; Karsenty, Gerard ; Olson, Eric N.</creatorcontrib><description>Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy. HDAC4-null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy, mimicking the phenotype that results from constitutive Runx2 expression in chondrocytes. Conversely, overexpression of HDAC4 in proliferating chondrocytes in vivo inhibits chondrocyte hypertrophy and differentiation, mimicking a Runx2 loss-of-function phenotype. These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/j.cell.2004.10.024</identifier><identifier>PMID: 15537544</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cell Differentiation ; Chondrocytes - enzymology ; Chondrocytes - pathology ; Core Binding Factor Alpha 1 Subunit ; Histone Deacetylases - physiology ; Hypertrophy - enzymology ; Mice ; Mice, Mutant Strains ; Models, Biological ; Neoplasm Proteins - antagonists & inhibitors ; Ossification, Heterotopic - pathology ; Osteogenesis ; Repressor Proteins - physiology ; Transcription Factors - antagonists & inhibitors</subject><ispartof>Cell, 2004-11, Vol.119 (4), p.555-566</ispartof><rights>2004 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-d5ae0c4be45b18e4e2629a21b63ce168a17675194633490721369c76779f3d1c3</citedby><cites>FETCH-LOGICAL-c493t-d5ae0c4be45b18e4e2629a21b63ce168a17675194633490721369c76779f3d1c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0092867404010347$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65534</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15537544$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Vega, Rick B.</creatorcontrib><creatorcontrib>Matsuda, Koichi</creatorcontrib><creatorcontrib>Oh, Junyoung</creatorcontrib><creatorcontrib>Barbosa, Ana C.</creatorcontrib><creatorcontrib>Yang, Xiangli</creatorcontrib><creatorcontrib>Meadows, Eric</creatorcontrib><creatorcontrib>McAnally, John</creatorcontrib><creatorcontrib>Pomajzl, Chris</creatorcontrib><creatorcontrib>Shelton, John M.</creatorcontrib><creatorcontrib>Richardson, James A.</creatorcontrib><creatorcontrib>Karsenty, Gerard</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><title>Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis</title><title>Cell</title><addtitle>Cell</addtitle><description>Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy. HDAC4-null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy, mimicking the phenotype that results from constitutive Runx2 expression in chondrocytes. Conversely, overexpression of HDAC4 in proliferating chondrocytes in vivo inhibits chondrocyte hypertrophy and differentiation, mimicking a Runx2 loss-of-function phenotype. These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy.</description><subject>Animals</subject><subject>Cell Differentiation</subject><subject>Chondrocytes - enzymology</subject><subject>Chondrocytes - pathology</subject><subject>Core Binding Factor Alpha 1 Subunit</subject><subject>Histone Deacetylases - physiology</subject><subject>Hypertrophy - enzymology</subject><subject>Mice</subject><subject>Mice, Mutant Strains</subject><subject>Models, Biological</subject><subject>Neoplasm Proteins - antagonists & inhibitors</subject><subject>Ossification, Heterotopic - pathology</subject><subject>Osteogenesis</subject><subject>Repressor Proteins - physiology</subject><subject>Transcription Factors - antagonists & inhibitors</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkDtPwzAYRS0EglL4AwwoE1uC7fgRSywoPIpUiQGYrcT52rqkcbATpPx7ErUSG0xXujr3DgehK4ITgom43SYG6jqhGLOxSDBlR2hGsJIxI5IeoxnGisaZkOwMnYewxRhnnPNTdEY4TyVnbIaWCxs610D0AIWBbqiLABGLctd03tUhyjeuqbwzQwfRYmjBj3W7GaKq97ZZR2-fUEPn1tBAsOECnayKOsDlIefo4-nxPV_Ey9fnl_x-GRum0i6ueAHYsBIYL0kGDKigqqCkFKkBIrKCSCE5UUykKVNYUpIKZcZOqlVaEZPO0c3-t_Xuq4fQ6Z0Nk4uiAdcHLSQWLJP0X5BIKUSmyAjSPWi8C8HDSrfe7go_aIL1JFtv9bTTk-ypG2WPo-vDe1_uoPqdHOyOwN0egFHGtwWvg7HQGKisB9Ppytm__n8AT5KPkA</recordid><startdate>20041112</startdate><enddate>20041112</enddate><creator>Vega, Rick B.</creator><creator>Matsuda, Koichi</creator><creator>Oh, Junyoung</creator><creator>Barbosa, Ana C.</creator><creator>Yang, Xiangli</creator><creator>Meadows, Eric</creator><creator>McAnally, John</creator><creator>Pomajzl, Chris</creator><creator>Shelton, John M.</creator><creator>Richardson, James A.</creator><creator>Karsenty, Gerard</creator><creator>Olson, Eric N.</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</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>7QP</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20041112</creationdate><title>Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis</title><author>Vega, Rick B. ; Matsuda, Koichi ; Oh, Junyoung ; Barbosa, Ana C. ; Yang, Xiangli ; Meadows, Eric ; McAnally, John ; Pomajzl, Chris ; Shelton, John M. ; Richardson, James A. ; Karsenty, Gerard ; Olson, Eric N.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-d5ae0c4be45b18e4e2629a21b63ce168a17675194633490721369c76779f3d1c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Cell Differentiation</topic><topic>Chondrocytes - enzymology</topic><topic>Chondrocytes - pathology</topic><topic>Core Binding Factor Alpha 1 Subunit</topic><topic>Histone Deacetylases - physiology</topic><topic>Hypertrophy - enzymology</topic><topic>Mice</topic><topic>Mice, Mutant Strains</topic><topic>Models, Biological</topic><topic>Neoplasm Proteins - antagonists & inhibitors</topic><topic>Ossification, Heterotopic - pathology</topic><topic>Osteogenesis</topic><topic>Repressor Proteins - physiology</topic><topic>Transcription Factors - antagonists & inhibitors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Vega, Rick B.</creatorcontrib><creatorcontrib>Matsuda, Koichi</creatorcontrib><creatorcontrib>Oh, Junyoung</creatorcontrib><creatorcontrib>Barbosa, Ana C.</creatorcontrib><creatorcontrib>Yang, Xiangli</creatorcontrib><creatorcontrib>Meadows, Eric</creatorcontrib><creatorcontrib>McAnally, John</creatorcontrib><creatorcontrib>Pomajzl, Chris</creatorcontrib><creatorcontrib>Shelton, John M.</creatorcontrib><creatorcontrib>Richardson, James A.</creatorcontrib><creatorcontrib>Karsenty, Gerard</creatorcontrib><creatorcontrib>Olson, Eric N.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Vega, Rick B.</au><au>Matsuda, Koichi</au><au>Oh, Junyoung</au><au>Barbosa, Ana C.</au><au>Yang, Xiangli</au><au>Meadows, Eric</au><au>McAnally, John</au><au>Pomajzl, Chris</au><au>Shelton, John M.</au><au>Richardson, James A.</au><au>Karsenty, Gerard</au><au>Olson, Eric N.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2004-11-12</date><risdate>2004</risdate><volume>119</volume><issue>4</issue><spage>555</spage><epage>566</epage><pages>555-566</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Histone deacetylases (HDACs) modulate cell growth and differentiation by governing chromatin structure and repressing the activity of specific transcription factors. We showed previously that HDAC9 acts as a negative regulator of cardiomyocyte hypertrophy and skeletal muscle differentiation. Here we report that HDAC4, which is expressed in prehypertrophic chondrocytes, regulates chondrocyte hypertrophy and endochondral bone formation by interacting with and inhibiting the activity of Runx2, a transcription factor necessary for chondrocyte hypertrophy. HDAC4-null mice display premature ossification of developing bones due to ectopic and early onset chondrocyte hypertrophy, mimicking the phenotype that results from constitutive Runx2 expression in chondrocytes. Conversely, overexpression of HDAC4 in proliferating chondrocytes in vivo inhibits chondrocyte hypertrophy and differentiation, mimicking a Runx2 loss-of-function phenotype. These results establish HDAC4 as a central regulator of chondrocyte hypertrophy and skeletogenesis and suggest general roles for class II HDACs in the control of cellular hypertrophy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>15537544</pmid><doi>10.1016/j.cell.2004.10.024</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0092-8674 |
| ispartof | Cell, 2004-11, Vol.119 (4), p.555-566 |
| issn | 0092-8674 1097-4172 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_67064872 |
| source | MEDLINE; Cell Press Free Archives; Elsevier ScienceDirect Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Animals Cell Differentiation Chondrocytes - enzymology Chondrocytes - pathology Core Binding Factor Alpha 1 Subunit Histone Deacetylases - physiology Hypertrophy - enzymology Mice Mice, Mutant Strains Models, Biological Neoplasm Proteins - antagonists & inhibitors Ossification, Heterotopic - pathology Osteogenesis Repressor Proteins - physiology Transcription Factors - antagonists & inhibitors |
| title | Histone Deacetylase 4 Controls Chondrocyte Hypertrophy during Skeletogenesis |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-16T08%3A10%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Histone%20Deacetylase%204%20Controls%20Chondrocyte%20Hypertrophy%20during%20Skeletogenesis&rft.jtitle=Cell&rft.au=Vega,%20Rick%20B.&rft.date=2004-11-12&rft.volume=119&rft.issue=4&rft.spage=555&rft.epage=566&rft.pages=555-566&rft.issn=0092-8674&rft.eissn=1097-4172&rft_id=info:doi/10.1016/j.cell.2004.10.024&rft_dat=%3Cproquest_cross%3E67064872%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=17766891&rft_id=info:pmid/15537544&rft_els_id=S0092867404010347&rfr_iscdi=true |