Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification

We evaluated the detailed expression patterns of Runx1 and Sox9 in various types of bone formation, and determined whether Runx1 expression was affected by Runx2 deficiency and Runx2 expression by Runx1 deficiency. Our results indicate that both Runx1 and Sox9 are intensely expressed in the future o...

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Veröffentlicht in:Journal of bone and mineral research 2004-10, Vol.19 (10), p.1671-1677
Hauptverfasser: Yamashiro, Takashi, Wang, Xiu‐Ping, Li, Zhe, Oya, Shinji, Åberg, Thomas, Fukunaga, Tomohiro, Kamioka, Hiroshi, Speck, Nancy A, Takano‐Yamamoto, Teruko, Thesleff, Irma
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container_end_page 1677
container_issue 10
container_start_page 1671
container_title Journal of bone and mineral research
container_volume 19
creator Yamashiro, Takashi
Wang, Xiu‐Ping
Li, Zhe
Oya, Shinji
Åberg, Thomas
Fukunaga, Tomohiro
Kamioka, Hiroshi
Speck, Nancy A
Takano‐Yamamoto, Teruko
Thesleff, Irma
description We evaluated the detailed expression patterns of Runx1 and Sox9 in various types of bone formation, and determined whether Runx1 expression was affected by Runx2 deficiency and Runx2 expression by Runx1 deficiency. Our results indicate that both Runx1 and Sox9 are intensely expressed in the future osteogenic cell compartment and in cartilage. The pattern of Runx1 and Sox9 expression suggests that both genes could potentially be involved in incipient intramembranous bone formation during craniofacial development. Introduction: Runx1, a gene essential for hematopoiesis, contains RUNX binding sites in its promoter region, suggesting possible cross‐regulation with Runx2 and potential regulatory roles in bone development. On the other hand, Sox9 is essential for chondrogenesis, and haploinsufficiency of Sox9 leads to premature ossification of the skeletal system. In this study, we studied the possible roles of Runx1 and Sox9 in bone development. Materials and Methods: Runx1, Runx2/Osf2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12–16 mice and in the endochondral bone‐forming regions of embryonic and postnatal long bones. In addition, we evaluated Runx2/Osf2 expression in the growing face of Runx1 knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Results: Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2‐expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in the regions of endochondral bone formation and in actively modeling or remodeling bone tissues in the long bones as well as in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2−/− mice compared with wildtype mice. Conclusions: Runx1 and Sox9 are specifically expressed in the osteogenic cell compartments in the craniofacial bones and the bone collar of long bones, and this expression is downregulated on terminal differentiation of osteoblasts. Our results suggest that Runx1 may play a role in incipient intramembranous bone formation.
doi_str_mv 10.1359/JBMR.040801
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Our results indicate that both Runx1 and Sox9 are intensely expressed in the future osteogenic cell compartment and in cartilage. The pattern of Runx1 and Sox9 expression suggests that both genes could potentially be involved in incipient intramembranous bone formation during craniofacial development. Introduction: Runx1, a gene essential for hematopoiesis, contains RUNX binding sites in its promoter region, suggesting possible cross‐regulation with Runx2 and potential regulatory roles in bone development. On the other hand, Sox9 is essential for chondrogenesis, and haploinsufficiency of Sox9 leads to premature ossification of the skeletal system. In this study, we studied the possible roles of Runx1 and Sox9 in bone development. Materials and Methods: Runx1, Runx2/Osf2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12–16 mice and in the endochondral bone‐forming regions of embryonic and postnatal long bones. In addition, we evaluated Runx2/Osf2 expression in the growing face of Runx1 knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Results: Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2‐expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in the regions of endochondral bone formation and in actively modeling or remodeling bone tissues in the long bones as well as in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2−/− mice compared with wildtype mice. Conclusions: Runx1 and Sox9 are specifically expressed in the osteogenic cell compartments in the craniofacial bones and the bone collar of long bones, and this expression is downregulated on terminal differentiation of osteoblasts. Our results suggest that Runx1 may play a role in incipient intramembranous bone formation.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1359/JBMR.040801</identifier><identifier>PMID: 15355562</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Washington, DC: John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</publisher><subject>Animals ; Biological and medical sciences ; Cartilage - metabolism ; Cell Adhesion Molecules - metabolism ; Core Binding Factor Alpha 1 Subunit ; Core Binding Factor Alpha 2 Subunit ; Core Binding Factor alpha Subunits ; DNA-Binding Proteins - metabolism ; Down-Regulation ; Facial Bones - embryology ; Facial Bones - metabolism ; Fundamental and applied biological sciences. Psychology ; High Mobility Group Proteins - metabolism ; In Situ Hybridization ; knockout/in ; Mice ; Mice, Knockout ; molecular pathways ; Neoplasm Proteins - deficiency ; Osteoblasts - physiology ; Osteogenesis - physiology ; Proto-Oncogene Proteins - metabolism ; rodent ; Skeleton and joints ; SOX9 Transcription Factor ; Transcription Factors - deficiency ; Transcription Factors - metabolism ; transcriptional factors ; Ulna - embryology ; Ulna - metabolism ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Journal of bone and mineral research, 2004-10, Vol.19 (10), p.1671-1677</ispartof><rights>Copyright © 2004 ASBMR</rights><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4990-dbfc3144958ee9dc5937d420b2e7417b98115af4dacc5f0f26ac049be709039e3</citedby><cites>FETCH-LOGICAL-c4990-dbfc3144958ee9dc5937d420b2e7417b98115af4dacc5f0f26ac049be709039e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1359%2FJBMR.040801$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1359%2FJBMR.040801$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1416,27922,27923,45572,45573</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=16164558$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15355562$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yamashiro, Takashi</creatorcontrib><creatorcontrib>Wang, Xiu‐Ping</creatorcontrib><creatorcontrib>Li, Zhe</creatorcontrib><creatorcontrib>Oya, Shinji</creatorcontrib><creatorcontrib>Åberg, Thomas</creatorcontrib><creatorcontrib>Fukunaga, Tomohiro</creatorcontrib><creatorcontrib>Kamioka, Hiroshi</creatorcontrib><creatorcontrib>Speck, Nancy A</creatorcontrib><creatorcontrib>Takano‐Yamamoto, Teruko</creatorcontrib><creatorcontrib>Thesleff, Irma</creatorcontrib><title>Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>We evaluated the detailed expression patterns of Runx1 and Sox9 in various types of bone formation, and determined whether Runx1 expression was affected by Runx2 deficiency and Runx2 expression by Runx1 deficiency. Our results indicate that both Runx1 and Sox9 are intensely expressed in the future osteogenic cell compartment and in cartilage. The pattern of Runx1 and Sox9 expression suggests that both genes could potentially be involved in incipient intramembranous bone formation during craniofacial development. Introduction: Runx1, a gene essential for hematopoiesis, contains RUNX binding sites in its promoter region, suggesting possible cross‐regulation with Runx2 and potential regulatory roles in bone development. On the other hand, Sox9 is essential for chondrogenesis, and haploinsufficiency of Sox9 leads to premature ossification of the skeletal system. In this study, we studied the possible roles of Runx1 and Sox9 in bone development. Materials and Methods: Runx1, Runx2/Osf2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12–16 mice and in the endochondral bone‐forming regions of embryonic and postnatal long bones. In addition, we evaluated Runx2/Osf2 expression in the growing face of Runx1 knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Results: Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2‐expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in the regions of endochondral bone formation and in actively modeling or remodeling bone tissues in the long bones as well as in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2−/− mice compared with wildtype mice. Conclusions: Runx1 and Sox9 are specifically expressed in the osteogenic cell compartments in the craniofacial bones and the bone collar of long bones, and this expression is downregulated on terminal differentiation of osteoblasts. Our results suggest that Runx1 may play a role in incipient intramembranous bone formation.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cartilage - metabolism</subject><subject>Cell Adhesion Molecules - metabolism</subject><subject>Core Binding Factor Alpha 1 Subunit</subject><subject>Core Binding Factor Alpha 2 Subunit</subject><subject>Core Binding Factor alpha Subunits</subject><subject>DNA-Binding Proteins - metabolism</subject><subject>Down-Regulation</subject><subject>Facial Bones - embryology</subject><subject>Facial Bones - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>High Mobility Group Proteins - metabolism</subject><subject>In Situ Hybridization</subject><subject>knockout/in</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>molecular pathways</subject><subject>Neoplasm Proteins - deficiency</subject><subject>Osteoblasts - physiology</subject><subject>Osteogenesis - physiology</subject><subject>Proto-Oncogene Proteins - metabolism</subject><subject>rodent</subject><subject>Skeleton and joints</subject><subject>SOX9 Transcription Factor</subject><subject>Transcription Factors - deficiency</subject><subject>Transcription Factors - metabolism</subject><subject>transcriptional factors</subject><subject>Ulna - embryology</subject><subject>Ulna - metabolism</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LtOwzAUgGELgWgpTOwoCywo5Zz4kniEiltVVFRgjhzHloxyKXEr2rfHpZW6gRd7-Hxs_YScIwyRcnkzvnuZDYFBBnhA-sgTGjOR4SHpQ5axGBjFHjnx_hMABBfimPSQU865SPpk_Np674rKRLO2Mj5qbTRbNiuMVFNGb-1KRq6Jnhvt5s40i3BadKo2ddGppl36aBouW6fVwrXNKTmyqvLmbLcPyMfD_fvoKZ5MH59Ht5NYMykhLgurKTImeWaMLDWXNC1ZAkViUoZpITNEriwrldbcgk2E0sBkYVKQQKWhA3K1nTvv2q-l8Yu8dl6bqlKNCX_Khch4ikj_hZiGRSkL8HoLdRdqdMbm887VqlvnCPmmcb5pnG8bB32xG7ssalPu7S5qAJc7oLxWlQ2ttPN7J1AwzrPg0q37dpVZ__Xm75kLDigREOgPDPyS1w</recordid><startdate>200410</startdate><enddate>200410</enddate><creator>Yamashiro, Takashi</creator><creator>Wang, Xiu‐Ping</creator><creator>Li, Zhe</creator><creator>Oya, Shinji</creator><creator>Åberg, Thomas</creator><creator>Fukunaga, Tomohiro</creator><creator>Kamioka, Hiroshi</creator><creator>Speck, Nancy A</creator><creator>Takano‐Yamamoto, Teruko</creator><creator>Thesleff, Irma</creator><general>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</general><general>American Society for Bone and Mineral Research</general><scope>IQODW</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>7X8</scope></search><sort><creationdate>200410</creationdate><title>Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification</title><author>Yamashiro, Takashi ; Wang, Xiu‐Ping ; Li, Zhe ; Oya, Shinji ; Åberg, Thomas ; Fukunaga, Tomohiro ; Kamioka, Hiroshi ; Speck, Nancy A ; Takano‐Yamamoto, Teruko ; Thesleff, Irma</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4990-dbfc3144958ee9dc5937d420b2e7417b98115af4dacc5f0f26ac049be709039e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cartilage - metabolism</topic><topic>Cell Adhesion Molecules - metabolism</topic><topic>Core Binding Factor Alpha 1 Subunit</topic><topic>Core Binding Factor Alpha 2 Subunit</topic><topic>Core Binding Factor alpha Subunits</topic><topic>DNA-Binding Proteins - metabolism</topic><topic>Down-Regulation</topic><topic>Facial Bones - embryology</topic><topic>Facial Bones - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>High Mobility Group Proteins - metabolism</topic><topic>In Situ Hybridization</topic><topic>knockout/in</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>molecular pathways</topic><topic>Neoplasm Proteins - deficiency</topic><topic>Osteoblasts - physiology</topic><topic>Osteogenesis - physiology</topic><topic>Proto-Oncogene Proteins - metabolism</topic><topic>rodent</topic><topic>Skeleton and joints</topic><topic>SOX9 Transcription Factor</topic><topic>Transcription Factors - deficiency</topic><topic>Transcription Factors - metabolism</topic><topic>transcriptional factors</topic><topic>Ulna - embryology</topic><topic>Ulna - metabolism</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yamashiro, Takashi</creatorcontrib><creatorcontrib>Wang, Xiu‐Ping</creatorcontrib><creatorcontrib>Li, Zhe</creatorcontrib><creatorcontrib>Oya, Shinji</creatorcontrib><creatorcontrib>Åberg, Thomas</creatorcontrib><creatorcontrib>Fukunaga, Tomohiro</creatorcontrib><creatorcontrib>Kamioka, Hiroshi</creatorcontrib><creatorcontrib>Speck, Nancy A</creatorcontrib><creatorcontrib>Takano‐Yamamoto, Teruko</creatorcontrib><creatorcontrib>Thesleff, Irma</creatorcontrib><collection>Pascal-Francis</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 &amp; Calcified Tissue Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yamashiro, Takashi</au><au>Wang, Xiu‐Ping</au><au>Li, Zhe</au><au>Oya, Shinji</au><au>Åberg, Thomas</au><au>Fukunaga, Tomohiro</au><au>Kamioka, Hiroshi</au><au>Speck, Nancy A</au><au>Takano‐Yamamoto, Teruko</au><au>Thesleff, Irma</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2004-10</date><risdate>2004</risdate><volume>19</volume><issue>10</issue><spage>1671</spage><epage>1677</epage><pages>1671-1677</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>We evaluated the detailed expression patterns of Runx1 and Sox9 in various types of bone formation, and determined whether Runx1 expression was affected by Runx2 deficiency and Runx2 expression by Runx1 deficiency. Our results indicate that both Runx1 and Sox9 are intensely expressed in the future osteogenic cell compartment and in cartilage. The pattern of Runx1 and Sox9 expression suggests that both genes could potentially be involved in incipient intramembranous bone formation during craniofacial development. Introduction: Runx1, a gene essential for hematopoiesis, contains RUNX binding sites in its promoter region, suggesting possible cross‐regulation with Runx2 and potential regulatory roles in bone development. On the other hand, Sox9 is essential for chondrogenesis, and haploinsufficiency of Sox9 leads to premature ossification of the skeletal system. In this study, we studied the possible roles of Runx1 and Sox9 in bone development. Materials and Methods: Runx1, Runx2/Osf2, and Sox9 expression was evaluated by in situ hybridization in the growing craniofacial bones of embryonic day (E)12–16 mice and in the endochondral bone‐forming regions of embryonic and postnatal long bones. In addition, we evaluated Runx2/Osf2 expression in the growing face of Runx1 knockout mice at E12.5 and Runx1 expression in Runx2 knockout mice at E14.5. Results: Runx1 and Sox9 were expressed in cartilage, and the regions of expression expanded to the neighboring Runx2‐expressing osteogenic regions. Expression of both Runx1 and Sox9 was markedly downregulated on ossification. Runx1 and Sox9 expression was absent in the regions of endochondral bone formation and in actively modeling or remodeling bone tissues in the long bones as well as in ossified craniofacial bones. Runx2 expression was not affected by gene disruption of Runx1, whereas the expression domains of Runx1 were extended in Runx2−/− mice compared with wildtype mice. Conclusions: Runx1 and Sox9 are specifically expressed in the osteogenic cell compartments in the craniofacial bones and the bone collar of long bones, and this expression is downregulated on terminal differentiation of osteoblasts. Our results suggest that Runx1 may play a role in incipient intramembranous bone formation.</abstract><cop>Washington, DC</cop><pub>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</pub><pmid>15355562</pmid><doi>10.1359/JBMR.040801</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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subjects Animals
Biological and medical sciences
Cartilage - metabolism
Cell Adhesion Molecules - metabolism
Core Binding Factor Alpha 1 Subunit
Core Binding Factor Alpha 2 Subunit
Core Binding Factor alpha Subunits
DNA-Binding Proteins - metabolism
Down-Regulation
Facial Bones - embryology
Facial Bones - metabolism
Fundamental and applied biological sciences. Psychology
High Mobility Group Proteins - metabolism
In Situ Hybridization
knockout/in
Mice
Mice, Knockout
molecular pathways
Neoplasm Proteins - deficiency
Osteoblasts - physiology
Osteogenesis - physiology
Proto-Oncogene Proteins - metabolism
rodent
Skeleton and joints
SOX9 Transcription Factor
Transcription Factors - deficiency
Transcription Factors - metabolism
transcriptional factors
Ulna - embryology
Ulna - metabolism
Vertebrates: osteoarticular system, musculoskeletal system
title Possible Roles of Runx1 and Sox9 in Incipient Intramembranous Ossification
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