Bril: A Novel Bone‐Specific Modulator of Mineralization
In the course of attempting to define the bone “secretome” using a signal‐trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene....
Gespeichert in:
Veröffentlicht in: | Journal of bone and mineral research 2008-09, Vol.23 (9), p.1497-1508 |
---|---|
Hauptverfasser: | , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1508 |
---|---|
container_issue | 9 |
container_start_page | 1497 |
container_title | Journal of bone and mineral research |
container_volume | 23 |
creator | Moffatt, Pierre Gaumond, Marie‐Helene Salois, Patrick Sellin, Karine Bessette, Marie‐Claude Godin, Éric de Oliveira, Paulo Tambasco Atkins, Gerald J Nanci, Antonio Thomas, Gethin |
description | In the course of attempting to define the bone “secretome” using a signal‐trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm‐like protein (Bril). Bril encodes a 14.8‐kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone‐specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus‐mediated Bril overexpression and lentivirus‐mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose‐dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation. |
doi_str_mv | 10.1359/jbmr.080412 |
format | Article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_69437290</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>20949963</sourcerecordid><originalsourceid>FETCH-LOGICAL-c4997-50e5c3a7a5b04988b53ac7050f0ac22eca3bf56d3e07eef1b36fb14667582c643</originalsourceid><addsrcrecordid>eNqF0LlOAzEQgGELgSAcFT3aBhq0ML7XdAniFAGJo155HVsyctbBTkBQ8Qg8I0_CokTQQTXNp5nRj9A2hgNMuTp8bMbpACpgmCyhHuaElkxUeBn1oKpYCYziNbSe8yMACC7EKlrDFWOEYtFDapB8OCr6xXV8tqEYxNZ-vn_cTazxzptiGEezoKcxFdEVQ9_apIN_01Mf20204nTIdmsxN9DD6cn98Xl5dXN2cdy_Kg1TSpYcLDdUS80bYKqqGk61kcDBgTaEWKNp47gYUQvSWocbKlyDmRCSV8QIRjfQ3nzvJMWnmc3TeuyzsSHo1sZZroViVBIF_0ICqvtI0A7uz6FJMedkXT1JfqzTa42h_k5afyet50k7vbNYO2vGdvRrFw07sLsAOhsdXNKt8fnHEeCKKCI7J-fuxQf7-tfN-nIwvOWCA6GgsKRfymiOoQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>20949963</pqid></control><display><type>article</type><title>Bril: A Novel Bone‐Specific Modulator of Mineralization</title><source>MEDLINE</source><source>Access via Wiley Online Library</source><source>Oxford University Press Journals All Titles (1996-Current)</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Moffatt, Pierre ; Gaumond, Marie‐Helene ; Salois, Patrick ; Sellin, Karine ; Bessette, Marie‐Claude ; Godin, Éric ; de Oliveira, Paulo Tambasco ; Atkins, Gerald J ; Nanci, Antonio ; Thomas, Gethin</creator><creatorcontrib>Moffatt, Pierre ; Gaumond, Marie‐Helene ; Salois, Patrick ; Sellin, Karine ; Bessette, Marie‐Claude ; Godin, Éric ; de Oliveira, Paulo Tambasco ; Atkins, Gerald J ; Nanci, Antonio ; Thomas, Gethin</creatorcontrib><description>In the course of attempting to define the bone “secretome” using a signal‐trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm‐like protein (Bril). Bril encodes a 14.8‐kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone‐specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus‐mediated Bril overexpression and lentivirus‐mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose‐dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1359/jbmr.080412</identifier><identifier>PMID: 18442316</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>Adenoviridae ; Amino Acid Sequence ; Animals ; Biological and medical sciences ; Biomarkers - metabolism ; Blotting, Western ; Bone and Bones - metabolism ; bone formation ; Calcification, Physiologic ; Cell Line ; Cloning, Molecular ; Embryo, Mammalian - cytology ; Embryo, Mammalian - metabolism ; Fluorescent Antibody Technique ; Fundamental and applied biological sciences. Psychology ; Gene Expression Profiling ; Humans ; In Situ Hybridization ; Lentivirus ; membrane protein ; Membrane Proteins - chemistry ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Mice ; mineralization ; Molecular Sequence Data ; novel bone gene ; Organ Specificity ; Osteoblasts - cytology ; Osteoblasts - metabolism ; osteoblast‐specific ; Proteins - chemistry ; Proteins - genetics ; Proteins - metabolism ; Rats ; Sequence Alignment ; Skeleton and joints ; Vertebrates: osteoarticular system, musculoskeletal system</subject><ispartof>Journal of bone and mineral research, 2008-09, Vol.23 (9), p.1497-1508</ispartof><rights>Copyright © 2008 ASBMR</rights><rights>2008 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4997-50e5c3a7a5b04988b53ac7050f0ac22eca3bf56d3e07eef1b36fb14667582c643</citedby><cites>FETCH-LOGICAL-c4997-50e5c3a7a5b04988b53ac7050f0ac22eca3bf56d3e07eef1b36fb14667582c643</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.080412$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1359%2Fjbmr.080412$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20592927$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18442316$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Moffatt, Pierre</creatorcontrib><creatorcontrib>Gaumond, Marie‐Helene</creatorcontrib><creatorcontrib>Salois, Patrick</creatorcontrib><creatorcontrib>Sellin, Karine</creatorcontrib><creatorcontrib>Bessette, Marie‐Claude</creatorcontrib><creatorcontrib>Godin, Éric</creatorcontrib><creatorcontrib>de Oliveira, Paulo Tambasco</creatorcontrib><creatorcontrib>Atkins, Gerald J</creatorcontrib><creatorcontrib>Nanci, Antonio</creatorcontrib><creatorcontrib>Thomas, Gethin</creatorcontrib><title>Bril: A Novel Bone‐Specific Modulator of Mineralization</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>In the course of attempting to define the bone “secretome” using a signal‐trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm‐like protein (Bril). Bril encodes a 14.8‐kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone‐specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus‐mediated Bril overexpression and lentivirus‐mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose‐dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.</description><subject>Adenoviridae</subject><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Blotting, Western</subject><subject>Bone and Bones - metabolism</subject><subject>bone formation</subject><subject>Calcification, Physiologic</subject><subject>Cell Line</subject><subject>Cloning, Molecular</subject><subject>Embryo, Mammalian - cytology</subject><subject>Embryo, Mammalian - metabolism</subject><subject>Fluorescent Antibody Technique</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression Profiling</subject><subject>Humans</subject><subject>In Situ Hybridization</subject><subject>Lentivirus</subject><subject>membrane protein</subject><subject>Membrane Proteins - chemistry</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - metabolism</subject><subject>Mice</subject><subject>mineralization</subject><subject>Molecular Sequence Data</subject><subject>novel bone gene</subject><subject>Organ Specificity</subject><subject>Osteoblasts - cytology</subject><subject>Osteoblasts - metabolism</subject><subject>osteoblast‐specific</subject><subject>Proteins - chemistry</subject><subject>Proteins - genetics</subject><subject>Proteins - metabolism</subject><subject>Rats</subject><subject>Sequence Alignment</subject><subject>Skeleton and joints</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqF0LlOAzEQgGELgSAcFT3aBhq0ML7XdAniFAGJo155HVsyctbBTkBQ8Qg8I0_CokTQQTXNp5nRj9A2hgNMuTp8bMbpACpgmCyhHuaElkxUeBn1oKpYCYziNbSe8yMACC7EKlrDFWOEYtFDapB8OCr6xXV8tqEYxNZ-vn_cTazxzptiGEezoKcxFdEVQ9_apIN_01Mf20204nTIdmsxN9DD6cn98Xl5dXN2cdy_Kg1TSpYcLDdUS80bYKqqGk61kcDBgTaEWKNp47gYUQvSWocbKlyDmRCSV8QIRjfQ3nzvJMWnmc3TeuyzsSHo1sZZroViVBIF_0ICqvtI0A7uz6FJMedkXT1JfqzTa42h_k5afyet50k7vbNYO2vGdvRrFw07sLsAOhsdXNKt8fnHEeCKKCI7J-fuxQf7-tfN-nIwvOWCA6GgsKRfymiOoQ</recordid><startdate>200809</startdate><enddate>200809</enddate><creator>Moffatt, Pierre</creator><creator>Gaumond, Marie‐Helene</creator><creator>Salois, Patrick</creator><creator>Sellin, Karine</creator><creator>Bessette, Marie‐Claude</creator><creator>Godin, Éric</creator><creator>de Oliveira, Paulo Tambasco</creator><creator>Atkins, Gerald J</creator><creator>Nanci, Antonio</creator><creator>Thomas, Gethin</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>200809</creationdate><title>Bril: A Novel Bone‐Specific Modulator of Mineralization</title><author>Moffatt, Pierre ; Gaumond, Marie‐Helene ; Salois, Patrick ; Sellin, Karine ; Bessette, Marie‐Claude ; Godin, Éric ; de Oliveira, Paulo Tambasco ; Atkins, Gerald J ; Nanci, Antonio ; Thomas, Gethin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4997-50e5c3a7a5b04988b53ac7050f0ac22eca3bf56d3e07eef1b36fb14667582c643</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Adenoviridae</topic><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Blotting, Western</topic><topic>Bone and Bones - metabolism</topic><topic>bone formation</topic><topic>Calcification, Physiologic</topic><topic>Cell Line</topic><topic>Cloning, Molecular</topic><topic>Embryo, Mammalian - cytology</topic><topic>Embryo, Mammalian - metabolism</topic><topic>Fluorescent Antibody Technique</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression Profiling</topic><topic>Humans</topic><topic>In Situ Hybridization</topic><topic>Lentivirus</topic><topic>membrane protein</topic><topic>Membrane Proteins - chemistry</topic><topic>Membrane Proteins - genetics</topic><topic>Membrane Proteins - metabolism</topic><topic>Mice</topic><topic>mineralization</topic><topic>Molecular Sequence Data</topic><topic>novel bone gene</topic><topic>Organ Specificity</topic><topic>Osteoblasts - cytology</topic><topic>Osteoblasts - metabolism</topic><topic>osteoblast‐specific</topic><topic>Proteins - chemistry</topic><topic>Proteins - genetics</topic><topic>Proteins - metabolism</topic><topic>Rats</topic><topic>Sequence Alignment</topic><topic>Skeleton and joints</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Moffatt, Pierre</creatorcontrib><creatorcontrib>Gaumond, Marie‐Helene</creatorcontrib><creatorcontrib>Salois, Patrick</creatorcontrib><creatorcontrib>Sellin, Karine</creatorcontrib><creatorcontrib>Bessette, Marie‐Claude</creatorcontrib><creatorcontrib>Godin, Éric</creatorcontrib><creatorcontrib>de Oliveira, Paulo Tambasco</creatorcontrib><creatorcontrib>Atkins, Gerald J</creatorcontrib><creatorcontrib>Nanci, Antonio</creatorcontrib><creatorcontrib>Thomas, Gethin</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 & 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>Moffatt, Pierre</au><au>Gaumond, Marie‐Helene</au><au>Salois, Patrick</au><au>Sellin, Karine</au><au>Bessette, Marie‐Claude</au><au>Godin, Éric</au><au>de Oliveira, Paulo Tambasco</au><au>Atkins, Gerald J</au><au>Nanci, Antonio</au><au>Thomas, Gethin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bril: A Novel Bone‐Specific Modulator of Mineralization</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2008-09</date><risdate>2008</risdate><volume>23</volume><issue>9</issue><spage>1497</spage><epage>1508</epage><pages>1497-1508</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>In the course of attempting to define the bone “secretome” using a signal‐trap screening approach, we identified a gene encoding a small membrane protein novel to osteoblasts. Although previously identified in silico as ifitm5, no localization or functional studies had been undertaken on this gene. We characterized the expression patterns and localization of this gene in vitro and in vivo and assessed its role in matrix mineralization in vitro. The bone specificity and shown role in mineralization led us to rename the gene bone restricted ifitm‐like protein (Bril). Bril encodes a 14.8‐kDa 134 amino acid protein with two transmembrane domains. Northern blot analysis showed bone‐specific expression with no expression in other embryonic or adult tissues. In situ hybridization and immunohistochemistry in mouse embryos showed expression localized on the developing bone. Screening of cell lines showed Bril expression to be highest in osteoblasts, associated with the onset of matrix maturation/mineralization, suggesting a role in bone formation. Functional evidence of a role in mineralization was shown by adenovirus‐mediated Bril overexpression and lentivirus‐mediated Bril shRNA knockdown in vitro. Elevated Bril resulted in dose‐dependent increases in mineralization in UMR106 and rat primary osteoblasts. Conversely, knockdown of Bril in MC3T3 osteoblasts resulted in reduced mineralization. Thus, we identified Bril as a novel osteoblast protein and showed a role in mineralization, possibly identifying a new regulatory pathway in bone formation.</abstract><cop>Washington, DC</cop><pub>John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)</pub><pmid>18442316</pmid><doi>10.1359/jbmr.080412</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 0884-0431 |
ispartof | Journal of bone and mineral research, 2008-09, Vol.23 (9), p.1497-1508 |
issn | 0884-0431 1523-4681 |
language | eng |
recordid | cdi_proquest_miscellaneous_69437290 |
source | MEDLINE; Access via Wiley Online Library; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Adenoviridae Amino Acid Sequence Animals Biological and medical sciences Biomarkers - metabolism Blotting, Western Bone and Bones - metabolism bone formation Calcification, Physiologic Cell Line Cloning, Molecular Embryo, Mammalian - cytology Embryo, Mammalian - metabolism Fluorescent Antibody Technique Fundamental and applied biological sciences. Psychology Gene Expression Profiling Humans In Situ Hybridization Lentivirus membrane protein Membrane Proteins - chemistry Membrane Proteins - genetics Membrane Proteins - metabolism Mice mineralization Molecular Sequence Data novel bone gene Organ Specificity Osteoblasts - cytology Osteoblasts - metabolism osteoblast‐specific Proteins - chemistry Proteins - genetics Proteins - metabolism Rats Sequence Alignment Skeleton and joints Vertebrates: osteoarticular system, musculoskeletal system |
title | Bril: A Novel Bone‐Specific Modulator of Mineralization |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-23T03%3A45%3A00IST&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=Bril:%20A%20Novel%20Bone%E2%80%90Specific%20Modulator%20of%20Mineralization&rft.jtitle=Journal%20of%20bone%20and%20mineral%20research&rft.au=Moffatt,%20Pierre&rft.date=2008-09&rft.volume=23&rft.issue=9&rft.spage=1497&rft.epage=1508&rft.pages=1497-1508&rft.issn=0884-0431&rft.eissn=1523-4681&rft.coden=JBMREJ&rft_id=info:doi/10.1359/jbmr.080412&rft_dat=%3Cproquest_cross%3E20949963%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=20949963&rft_id=info:pmid/18442316&rfr_iscdi=true |