Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism
We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied t...
Gespeichert in:
| Veröffentlicht in: | Molecular endocrinology (Baltimore, Md.) Md.), 2010-06, Vol.24 (6), p.1267-1273 |
|---|---|
| Hauptverfasser: | , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1273 |
|---|---|
| container_issue | 6 |
| container_start_page | 1267 |
| container_title | Molecular endocrinology (Baltimore, Md.) |
| container_volume | 24 |
| creator | Endo, Toyoshi Kobayashi, Tetsuro |
| description | We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I− symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism.
Normal thyrocytes express Runx2, an osteoblast-specific transcription factor. Runx2 deficiency in mice causes decreased thyroglobulin expression in thyroid glands and a novel type of hypothyroidism. |
| doi_str_mv | 10.1210/me.2010-0056 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5417472</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1210/me.2010-0056</oup_id><sourcerecordid>733105433</sourcerecordid><originalsourceid>FETCH-LOGICAL-c459t-e008c48eb54c5668124c1d8985ef12aab2691b778cc507f6f5d692eb55a16ec83</originalsourceid><addsrcrecordid>eNp1kU1LxDAQhoMoun7cPEtvXqwmadImF0HWT1AEWc8hTacaaZOabMX993bddVXQ0xzm4ZnhfRHaJ_iYUIJPWjimmOAUY56voRGRjKVSkmIdjbAQIhUCyy20HeMLxoRxQTbRFsVZwWkmR-jxoXfvNDmH2hoLzswS65I7ayAZ6z5CHDYmgI5QJZPnWfBPjS_7ZmAu3rsAMVrvEu2q5HrW-ekcsJWN7S7aqHUTYW85d9Dj5cVkfJ3e3l_djM9uU8O4nKaAsTBMQMmZ4XkuCGWGVEIKDjWhWpc0l6QsCmEMx0Wd17zKJR1wrkkORmQ76HTh7fqyhcqAmwbdqC7YVoeZ8tqq3xtnn9WTf1OckYIVdBAcLgXBv_YQp6q10UDTaAe-j6rIMoI5y7KBPFqQJvgYA9SrKwSreRGqBTUvQs2LGPCDn5-t4K_kvy_7vvtPlS5V2YIEV3kTrIPP5NWL74Mb0v37gQ_L3qI6</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>733105433</pqid></control><display><type>article</type><title>Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>Alma/SFX Local Collection</source><creator>Endo, Toyoshi ; Kobayashi, Tetsuro</creator><creatorcontrib>Endo, Toyoshi ; Kobayashi, Tetsuro</creatorcontrib><description>We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I− symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism.
Normal thyrocytes express Runx2, an osteoblast-specific transcription factor. Runx2 deficiency in mice causes decreased thyroglobulin expression in thyroid glands and a novel type of hypothyroidism.</description><identifier>ISSN: 0888-8809</identifier><identifier>EISSN: 1944-9917</identifier><identifier>DOI: 10.1210/me.2010-0056</identifier><identifier>PMID: 20375239</identifier><language>eng</language><publisher>United States: Endocrine Society</publisher><subject>Animals ; Core Binding Factor Alpha 1 Subunit - deficiency ; Core Binding Factor Alpha 1 Subunit - genetics ; Core Binding Factor Alpha 1 Subunit - metabolism ; Gene Silencing ; Hypothyroidism - metabolism ; Hypothyroidism - physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Organ Specificity ; Original Research ; Promoter Regions, Genetic - genetics ; Protein Binding ; RNA, Small Interfering - metabolism ; Thyroglobulin - genetics ; Thyroglobulin - metabolism ; Thyroid Function Tests ; Thyroid Gland - growth & development ; Thyroid Gland - pathology ; Thyroid Gland - physiopathology</subject><ispartof>Molecular endocrinology (Baltimore, Md.), 2010-06, Vol.24 (6), p.1267-1273</ispartof><rights>Copyright © 2010 by The Endocrine Society 2010</rights><rights>2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c459t-e008c48eb54c5668124c1d8985ef12aab2691b778cc507f6f5d692eb55a16ec83</citedby><cites>FETCH-LOGICAL-c459t-e008c48eb54c5668124c1d8985ef12aab2691b778cc507f6f5d692eb55a16ec83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,778,782,883,27907,27908</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20375239$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Endo, Toyoshi</creatorcontrib><creatorcontrib>Kobayashi, Tetsuro</creatorcontrib><title>Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism</title><title>Molecular endocrinology (Baltimore, Md.)</title><addtitle>Mol Endocrinol</addtitle><description>We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I− symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism.
Normal thyrocytes express Runx2, an osteoblast-specific transcription factor. Runx2 deficiency in mice causes decreased thyroglobulin expression in thyroid glands and a novel type of hypothyroidism.</description><subject>Animals</subject><subject>Core Binding Factor Alpha 1 Subunit - deficiency</subject><subject>Core Binding Factor Alpha 1 Subunit - genetics</subject><subject>Core Binding Factor Alpha 1 Subunit - metabolism</subject><subject>Gene Silencing</subject><subject>Hypothyroidism - metabolism</subject><subject>Hypothyroidism - physiopathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Organ Specificity</subject><subject>Original Research</subject><subject>Promoter Regions, Genetic - genetics</subject><subject>Protein Binding</subject><subject>RNA, Small Interfering - metabolism</subject><subject>Thyroglobulin - genetics</subject><subject>Thyroglobulin - metabolism</subject><subject>Thyroid Function Tests</subject><subject>Thyroid Gland - growth & development</subject><subject>Thyroid Gland - pathology</subject><subject>Thyroid Gland - physiopathology</subject><issn>0888-8809</issn><issn>1944-9917</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1LxDAQhoMoun7cPEtvXqwmadImF0HWT1AEWc8hTacaaZOabMX993bddVXQ0xzm4ZnhfRHaJ_iYUIJPWjimmOAUY56voRGRjKVSkmIdjbAQIhUCyy20HeMLxoRxQTbRFsVZwWkmR-jxoXfvNDmH2hoLzswS65I7ayAZ6z5CHDYmgI5QJZPnWfBPjS_7ZmAu3rsAMVrvEu2q5HrW-ekcsJWN7S7aqHUTYW85d9Dj5cVkfJ3e3l_djM9uU8O4nKaAsTBMQMmZ4XkuCGWGVEIKDjWhWpc0l6QsCmEMx0Wd17zKJR1wrkkORmQ76HTh7fqyhcqAmwbdqC7YVoeZ8tqq3xtnn9WTf1OckYIVdBAcLgXBv_YQp6q10UDTaAe-j6rIMoI5y7KBPFqQJvgYA9SrKwSreRGqBTUvQs2LGPCDn5-t4K_kvy_7vvtPlS5V2YIEV3kTrIPP5NWL74Mb0v37gQ_L3qI6</recordid><startdate>201006</startdate><enddate>201006</enddate><creator>Endo, Toyoshi</creator><creator>Kobayashi, Tetsuro</creator><general>Endocrine Society</general><general>Oxford University Press</general><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>201006</creationdate><title>Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism</title><author>Endo, Toyoshi ; Kobayashi, Tetsuro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c459t-e008c48eb54c5668124c1d8985ef12aab2691b778cc507f6f5d692eb55a16ec83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Core Binding Factor Alpha 1 Subunit - deficiency</topic><topic>Core Binding Factor Alpha 1 Subunit - genetics</topic><topic>Core Binding Factor Alpha 1 Subunit - metabolism</topic><topic>Gene Silencing</topic><topic>Hypothyroidism - metabolism</topic><topic>Hypothyroidism - physiopathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Organ Specificity</topic><topic>Original Research</topic><topic>Promoter Regions, Genetic - genetics</topic><topic>Protein Binding</topic><topic>RNA, Small Interfering - metabolism</topic><topic>Thyroglobulin - genetics</topic><topic>Thyroglobulin - metabolism</topic><topic>Thyroid Function Tests</topic><topic>Thyroid Gland - growth & development</topic><topic>Thyroid Gland - pathology</topic><topic>Thyroid Gland - physiopathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Endo, Toyoshi</creatorcontrib><creatorcontrib>Kobayashi, Tetsuro</creatorcontrib><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>Molecular endocrinology (Baltimore, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Endo, Toyoshi</au><au>Kobayashi, Tetsuro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism</atitle><jtitle>Molecular endocrinology (Baltimore, Md.)</jtitle><addtitle>Mol Endocrinol</addtitle><date>2010-06</date><risdate>2010</risdate><volume>24</volume><issue>6</issue><spage>1267</spage><epage>1273</epage><pages>1267-1273</pages><issn>0888-8809</issn><eissn>1944-9917</eissn><abstract>We recently reported on the overexpression of Runx2 (Cbfa1/AML3), an osteoblast-specific transcription factor, in human papillary thyroid cancer tissues. We report here that normal thyrocytes also express Runx2 and that Runx2+/− mice are in a hypothyroid state. To clarify the mechanism, we studied the effects of small interfering RNA-mediated silencing of Runx2 on thyroid-specific gene expression in FRTL-5 cells. Lowering the levels of Runx2 had no effect on the amount of Na+/I− symporter mRNA but markedly decreased the amount of thyroglobulin (Tg) mRNA. A Runx2 binding consensus sequence is present on the Tg gene promoter, and gel-shift assay revealed that Runx2 binds to this region. Reporter assay showed that deletion of the region or introduction of a mutation into the binding site significantly impairs promoter function. These results indicate that Runx2 deficiency in mice causes decreased Tg expression and a novel type of hypothyroidism.
Normal thyrocytes express Runx2, an osteoblast-specific transcription factor. Runx2 deficiency in mice causes decreased thyroglobulin expression in thyroid glands and a novel type of hypothyroidism.</abstract><cop>United States</cop><pub>Endocrine Society</pub><pmid>20375239</pmid><doi>10.1210/me.2010-0056</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0888-8809 |
| ispartof | Molecular endocrinology (Baltimore, Md.), 2010-06, Vol.24 (6), p.1267-1273 |
| issn | 0888-8809 1944-9917 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5417472 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection |
| subjects | Animals Core Binding Factor Alpha 1 Subunit - deficiency Core Binding Factor Alpha 1 Subunit - genetics Core Binding Factor Alpha 1 Subunit - metabolism Gene Silencing Hypothyroidism - metabolism Hypothyroidism - physiopathology Male Mice Mice, Inbred C57BL Organ Specificity Original Research Promoter Regions, Genetic - genetics Protein Binding RNA, Small Interfering - metabolism Thyroglobulin - genetics Thyroglobulin - metabolism Thyroid Function Tests Thyroid Gland - growth & development Thyroid Gland - pathology Thyroid Gland - physiopathology |
| title | Runx2 Deficiency in Mice Causes Decreased Thyroglobulin Expression and Hypothyroidism |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T22%3A32%3A18IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Runx2%20Deficiency%20in%20Mice%20Causes%20Decreased%20Thyroglobulin%20Expression%20and%20Hypothyroidism&rft.jtitle=Molecular%20endocrinology%20(Baltimore,%20Md.)&rft.au=Endo,%20Toyoshi&rft.date=2010-06&rft.volume=24&rft.issue=6&rft.spage=1267&rft.epage=1273&rft.pages=1267-1273&rft.issn=0888-8809&rft.eissn=1944-9917&rft_id=info:doi/10.1210/me.2010-0056&rft_dat=%3Cproquest_pubme%3E733105433%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=733105433&rft_id=info:pmid/20375239&rft_oup_id=10.1210/me.2010-0056&rfr_iscdi=true |