Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects
ABSTRACT The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during inci...
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| Veröffentlicht in: | Journal of bone and mineral research 2016-01, Vol.31 (1), p.152-162 |
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| creator | Jheon, Andrew H Prochazkova, Michaela Meng, Bo Wen, Timothy Lim, Young‐Jun Naveau, Adrien Espinoza, Ruben Cox, Timothy C Sone, Eli D Ganss, Bernhard Siebel, Christian W Klein, Ophir D |
| description | ABSTRACT
The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel‐forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome‐specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast‐SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome‐specific components, and that the mouse incisor provides a model system to dissect Jag‐Notch signaling mechanisms in the context of mineralized tissue renewal. © 2015 American Society for Bone and Mineral Research. |
| doi_str_mv | 10.1002/jbmr.2591 |
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The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel‐forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome‐specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast‐SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome‐specific components, and that the mouse incisor provides a model system to dissect Jag‐Notch signaling mechanisms in the context of mineralized tissue renewal. © 2015 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.2591</identifier><identifier>PMID: 26179131</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>AMELOBLAST ; Ameloblasts - metabolism ; Ameloblasts - pathology ; AMELOGENESIS ; Animals ; Dental Enamel - metabolism ; Dental Enamel - pathology ; Desmosomes - metabolism ; Desmosomes - pathology ; Incisor - metabolism ; Incisor - pathology ; JAG ; Mice ; NOTCH ; Receptors, Notch ; Signal Transduction ; STRATUM INTERMEDIUM ; TOOTH DEVELOPMENT ; Tooth Diseases</subject><ispartof>Journal of bone and mineral research, 2016-01, Vol.31 (1), p.152-162</ispartof><rights>2015 American Society for Bone and Mineral Research</rights><rights>2015 American Society for Bone and Mineral Research.</rights><rights>2016 American Society for Bone and Mineral Research</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c6121-4eab1a7b1149ee89d5d8d03585302f53364f5dcc40c0da22f924550d1ed7247c3</citedby><cites>FETCH-LOGICAL-c6121-4eab1a7b1149ee89d5d8d03585302f53364f5dcc40c0da22f924550d1ed7247c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.2591$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.2591$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,780,784,885,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26179131$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jheon, Andrew H</creatorcontrib><creatorcontrib>Prochazkova, Michaela</creatorcontrib><creatorcontrib>Meng, Bo</creatorcontrib><creatorcontrib>Wen, Timothy</creatorcontrib><creatorcontrib>Lim, Young‐Jun</creatorcontrib><creatorcontrib>Naveau, Adrien</creatorcontrib><creatorcontrib>Espinoza, Ruben</creatorcontrib><creatorcontrib>Cox, Timothy C</creatorcontrib><creatorcontrib>Sone, Eli D</creatorcontrib><creatorcontrib>Ganss, Bernhard</creatorcontrib><creatorcontrib>Siebel, Christian W</creatorcontrib><creatorcontrib>Klein, Ophir D</creatorcontrib><title>Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel‐forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome‐specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast‐SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome‐specific components, and that the mouse incisor provides a model system to dissect Jag‐Notch signaling mechanisms in the context of mineralized tissue renewal. © 2015 American Society for Bone and Mineral Research.</description><subject>AMELOBLAST</subject><subject>Ameloblasts - metabolism</subject><subject>Ameloblasts - pathology</subject><subject>AMELOGENESIS</subject><subject>Animals</subject><subject>Dental Enamel - metabolism</subject><subject>Dental Enamel - pathology</subject><subject>Desmosomes - metabolism</subject><subject>Desmosomes - pathology</subject><subject>Incisor - metabolism</subject><subject>Incisor - pathology</subject><subject>JAG</subject><subject>Mice</subject><subject>NOTCH</subject><subject>Receptors, Notch</subject><subject>Signal Transduction</subject><subject>STRATUM INTERMEDIUM</subject><subject>TOOTH DEVELOPMENT</subject><subject>Tooth Diseases</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkU1v1DAQhi0EokvhwB9AlrjAIa3HX0kuSNAWWLQFaYGz5TiTXa-ydrETqv57ErZUgITE6T3Mo0cz8xLyFNgJMMZPd80-nXBVwz2yAMVFIXUF98mCVZUsmBRwRB7lvGOMaaX1Q3LENZQ1CFiQ9TJsfeMHHwONHf0YB7eln_0m2N6HDT0f0xyXccxIl8H5HBNdY8Br29MV2jbTIdKLYPfY03Ps0A35MXnQ2T7jk9s8Jl_fXnw5e1-sPr1bnr1eFU4Dh0KibcCWDYCsEau6VW3VMqEqJRjvlBBadqp1TjLHWst5V3OpFGsB25LL0olj8urgvRqbPbYOw5Bsb66S39t0Y6L15s9J8Fuzid-NrCSDspoEL24FKX4bMQ9m77PDvrcBp4MNlKXWetpD_weqWc1higl9_he6i2Oa_jlTqhYMQPCJenmgXIo5J-zu9gZm5lLNXKqZS53YZ78fekf-anECTg_Ate_x5t8m8-HN5fqn8gdeCaro</recordid><startdate>201601</startdate><enddate>201601</enddate><creator>Jheon, Andrew H</creator><creator>Prochazkova, Michaela</creator><creator>Meng, Bo</creator><creator>Wen, Timothy</creator><creator>Lim, Young‐Jun</creator><creator>Naveau, Adrien</creator><creator>Espinoza, Ruben</creator><creator>Cox, Timothy C</creator><creator>Sone, Eli D</creator><creator>Ganss, Bernhard</creator><creator>Siebel, Christian W</creator><creator>Klein, Ophir D</creator><general>Wiley Subscription Services, Inc</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>7QP</scope><scope>7TS</scope><scope>K9.</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201601</creationdate><title>Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects</title><author>Jheon, Andrew H ; Prochazkova, Michaela ; Meng, Bo ; Wen, Timothy ; Lim, Young‐Jun ; Naveau, Adrien ; Espinoza, Ruben ; Cox, Timothy C ; Sone, Eli D ; Ganss, Bernhard ; Siebel, Christian W ; Klein, Ophir D</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6121-4eab1a7b1149ee89d5d8d03585302f53364f5dcc40c0da22f924550d1ed7247c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>AMELOBLAST</topic><topic>Ameloblasts - metabolism</topic><topic>Ameloblasts - pathology</topic><topic>AMELOGENESIS</topic><topic>Animals</topic><topic>Dental Enamel - metabolism</topic><topic>Dental Enamel - pathology</topic><topic>Desmosomes - metabolism</topic><topic>Desmosomes - pathology</topic><topic>Incisor - metabolism</topic><topic>Incisor - pathology</topic><topic>JAG</topic><topic>Mice</topic><topic>NOTCH</topic><topic>Receptors, Notch</topic><topic>Signal Transduction</topic><topic>STRATUM INTERMEDIUM</topic><topic>TOOTH DEVELOPMENT</topic><topic>Tooth Diseases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jheon, Andrew H</creatorcontrib><creatorcontrib>Prochazkova, Michaela</creatorcontrib><creatorcontrib>Meng, Bo</creatorcontrib><creatorcontrib>Wen, Timothy</creatorcontrib><creatorcontrib>Lim, Young‐Jun</creatorcontrib><creatorcontrib>Naveau, Adrien</creatorcontrib><creatorcontrib>Espinoza, Ruben</creatorcontrib><creatorcontrib>Cox, Timothy C</creatorcontrib><creatorcontrib>Sone, Eli D</creatorcontrib><creatorcontrib>Ganss, Bernhard</creatorcontrib><creatorcontrib>Siebel, Christian W</creatorcontrib><creatorcontrib>Klein, Ophir D</creatorcontrib><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>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jheon, Andrew H</au><au>Prochazkova, Michaela</au><au>Meng, Bo</au><au>Wen, Timothy</au><au>Lim, Young‐Jun</au><au>Naveau, Adrien</au><au>Espinoza, Ruben</au><au>Cox, Timothy C</au><au>Sone, Eli D</au><au>Ganss, Bernhard</au><au>Siebel, Christian W</au><au>Klein, Ophir D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2016-01</date><risdate>2016</risdate><volume>31</volume><issue>1</issue><spage>152</spage><epage>162</epage><pages>152-162</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>ABSTRACT
The continuously growing rodent incisor is an emerging model for the study of renewal of mineralized tissues by adult stem cells. Although the Bmp, Fgf, Shh, and Wnt pathways have been studied in this organ previously, relatively little is known about the role of Notch signaling during incisor renewal. Notch signaling components are expressed in enamel‐forming ameloblasts and the underlying stratum intermedium (SI), which suggested distinct roles in incisor renewal and enamel mineralization. Here, we injected adult mice with inhibitory antibodies against several components of the Notch pathway. This blockade led to defects in the interaction between ameloblasts and the SI cells, which ultimately affected enamel formation. Furthermore, Notch signaling inhibition led to the downregulation of desmosome‐specific proteins such as PERP and desmoplakin, consistent with the importance of desmosomes in the integrity of ameloblast‐SI attachment and enamel formation. Together, our data demonstrate that Notch signaling is critical for proper enamel formation during incisor renewal, in part by regulating desmosome‐specific components, and that the mouse incisor provides a model system to dissect Jag‐Notch signaling mechanisms in the context of mineralized tissue renewal. © 2015 American Society for Bone and Mineral Research.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>26179131</pmid><doi>10.1002/jbmr.2591</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Oxford University Press Journals All Titles (1996-Current); EZB-FREE-00999 freely available EZB journals; Wiley Online Library All Journals |
| subjects | AMELOBLAST Ameloblasts - metabolism Ameloblasts - pathology AMELOGENESIS Animals Dental Enamel - metabolism Dental Enamel - pathology Desmosomes - metabolism Desmosomes - pathology Incisor - metabolism Incisor - pathology JAG Mice NOTCH Receptors, Notch Signal Transduction STRATUM INTERMEDIUM TOOTH DEVELOPMENT Tooth Diseases |
| title | Inhibition of Notch Signaling During Mouse Incisor Renewal Leads to Enamel Defects |
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