Wnt-RhoA signaling is involved in dental enamel development

Peng L, Li Y, Shusterman K, Kuehl M, Gibson CW. Wnt‐RhoA signaling is involved in dental enamel development. 
 Eur J Oral Sci 2011; 119 (Suppl. 1): 41–49. © 2011 Eur J Oral Sci Transgenic mice that express dominant‐negative RhoA (RhoADN) in ameloblasts have hypoplastic enamel with defects in molar c...

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Veröffentlicht in:European journal of oral sciences 2011-12, Vol.119 (s1), p.41-49
Hauptverfasser: Peng, Li, Li, Yong, Shusterman, Kate, Kuehl, Melissa, Gibson, Carolyn W.
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container_title European journal of oral sciences
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creator Peng, Li
Li, Yong
Shusterman, Kate
Kuehl, Melissa
Gibson, Carolyn W.
description Peng L, Li Y, Shusterman K, Kuehl M, Gibson CW. Wnt‐RhoA signaling is involved in dental enamel development. 
 Eur J Oral Sci 2011; 119 (Suppl. 1): 41–49. © 2011 Eur J Oral Sci Transgenic mice that express dominant‐negative RhoA (RhoADN) in ameloblasts have hypoplastic enamel with defects in molar cusps. β‐catenin and Wnt5a were up‐regulated in enamel organs of RhoADN transgenic mice, which indicated that both canonical and non‐canonical Wnt pathways are implicated in the process of enamel defect formation. It was hypothesized that expression of RhoADN in ameloblasts interfered with normal enamel development through the pathways that were induced by fluoride. The Wnt and RhoA pathways were further investigated in an ameloblast‐lineage cell line (ALC) by treatment with sodium fluoride (NaF). The activities of RhoA and Rho‐associated protein kinase (ROCK) II decreased significantly by 8–12 hours, similar to decreased activity in RhoADN transgenic mice. Both canonical and non‐canonical Wnt pathways were activated by treatment with NaF, which was verified by western blotting and the β‐catenin‐TCF/LEF (T cell factor lymphanoid/enhancer factor) reporter gene (TOPflash) assay. β‐catenin localization to both cytoplasm and nucleus was up‐regulated in NaF‐treated ALC, while Gsk‐3β, the negative regulator of the Wnt pathway, showed a decreased pattern of expression. The current results indicate that both Wnt and RhoA pathways are implicated in fluoride‐induced signaling transductions in the ALC as well as in the development of enamel defects in RhoADN transgenic mice.
doi_str_mv 10.1111/j.1600-0722.2011.00880.x
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 Eur J Oral Sci 2011; 119 (Suppl. 1): 41–49. © 2011 Eur J Oral Sci Transgenic mice that express dominant‐negative RhoA (RhoADN) in ameloblasts have hypoplastic enamel with defects in molar cusps. β‐catenin and Wnt5a were up‐regulated in enamel organs of RhoADN transgenic mice, which indicated that both canonical and non‐canonical Wnt pathways are implicated in the process of enamel defect formation. It was hypothesized that expression of RhoADN in ameloblasts interfered with normal enamel development through the pathways that were induced by fluoride. The Wnt and RhoA pathways were further investigated in an ameloblast‐lineage cell line (ALC) by treatment with sodium fluoride (NaF). The activities of RhoA and Rho‐associated protein kinase (ROCK) II decreased significantly by 8–12 hours, similar to decreased activity in RhoADN transgenic mice. Both canonical and non‐canonical Wnt pathways were activated by treatment with NaF, which was verified by western blotting and the β‐catenin‐TCF/LEF (T cell factor lymphanoid/enhancer factor) reporter gene (TOPflash) assay. β‐catenin localization to both cytoplasm and nucleus was up‐regulated in NaF‐treated ALC, while Gsk‐3β, the negative regulator of the Wnt pathway, showed a decreased pattern of expression. The current results indicate that both Wnt and RhoA pathways are implicated in fluoride‐induced signaling transductions in the ALC as well as in the development of enamel defects in RhoADN transgenic mice.</description><subject>Ameloblasts - drug effects</subject><subject>Ameloblasts - physiology</subject><subject>Amelogenesis - genetics</subject><subject>Amelogenin - biosynthesis</subject><subject>Amelogenin - genetics</subject><subject>Animals</subject><subject>beta Catenin - biosynthesis</subject><subject>beta Catenin - genetics</subject><subject>Cell Line</subject><subject>dental enamel</subject><subject>Dental Enamel Hypoplasia - genetics</subject><subject>Dentistry</subject><subject>Enamel Organ - drug effects</subject><subject>Enamel Organ - physiology</subject><subject>Gene Expression Regulation, Developmental</subject><subject>Genes, Reporter</subject><subject>GTP-Binding Protein Regulators - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>rho GTP-Binding Proteins - genetics</subject><subject>rho GTP-Binding Proteins - physiology</subject><subject>rho-Associated Kinases - genetics</subject><subject>RhoA</subject><subject>rhoA GTP-Binding Protein - genetics</subject><subject>rhoA GTP-Binding Protein - physiology</subject><subject>RhoADN transgenic mice</subject><subject>Signal Transduction - drug effects</subject><subject>Signal Transduction - genetics</subject><subject>Sodium Fluoride - pharmacology</subject><subject>Wnt</subject><subject>Wnt Proteins - biosynthesis</subject><subject>Wnt Proteins - genetics</subject><subject>Wnt Signaling Pathway - drug effects</subject><subject>Wnt Signaling Pathway - genetics</subject><subject>Wnt-5a Protein</subject><issn>0909-8836</issn><issn>1600-0722</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNUV1v0zAUtRCIlcFfQHmDl4R77cQfAiFN01YQg0kMNN6unMTtXJykxG3p_j3uOip4Qfjl2veec3zsw1iGUGBarxYFSoAcFOcFB8QCQGsotg_Y5DB4yCZgwORaC3nEnsS4AECBRj1mR5zzUnBeTdjr636Vf74ZTrLo570Nvp9nPma-3wxh49q0yVrXr2zIXG87F9Jp48Kw7FLzKXs0syG6Z_f1mH09P_ty-i6_uJy-Pz25yBuZHOSVgRp0VdaNlrwFidhUEluhJJSthlaVRs_MTJStQmMRS2m4c2hqkErX2opj9navu1zXnWubdPVoAy1H39nxlgbr6e9J729oPmxIcJX-RSeBF_cC4_Bj7eKKOh8bF4Lt3bCOZFAlfyBMQr78JxKFMQYEakhQvYc24xDj6GYHQwi0S4kWtAuDdmHQLiW6S4m2ifr8zwcdiL9jSYA3e8BPH9ztfwvT2eWVvrOW7-k-rtz2QLfjd5JKqIquP03pI5x_41cfpqTEL7cardo</recordid><startdate>201112</startdate><enddate>201112</enddate><creator>Peng, Li</creator><creator>Li, Yong</creator><creator>Shusterman, Kate</creator><creator>Kuehl, Melissa</creator><creator>Gibson, Carolyn W.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</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><scope>5PM</scope></search><sort><creationdate>201112</creationdate><title>Wnt-RhoA signaling is involved in dental enamel development</title><author>Peng, Li ; Li, Yong ; Shusterman, Kate ; Kuehl, Melissa ; Gibson, Carolyn W.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6090-590b0854bc862d0611c561d37604d80d7498f9f34d719a114692ee19b0678b8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Ameloblasts - drug effects</topic><topic>Ameloblasts - physiology</topic><topic>Amelogenesis - genetics</topic><topic>Amelogenin - biosynthesis</topic><topic>Amelogenin - genetics</topic><topic>Animals</topic><topic>beta Catenin - biosynthesis</topic><topic>beta Catenin - genetics</topic><topic>Cell Line</topic><topic>dental enamel</topic><topic>Dental Enamel Hypoplasia - genetics</topic><topic>Dentistry</topic><topic>Enamel Organ - drug effects</topic><topic>Enamel Organ - physiology</topic><topic>Gene Expression Regulation, Developmental</topic><topic>Genes, Reporter</topic><topic>GTP-Binding Protein Regulators - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>rho GTP-Binding Proteins - genetics</topic><topic>rho GTP-Binding Proteins - physiology</topic><topic>rho-Associated Kinases - genetics</topic><topic>RhoA</topic><topic>rhoA GTP-Binding Protein - genetics</topic><topic>rhoA GTP-Binding Protein - physiology</topic><topic>RhoADN transgenic mice</topic><topic>Signal Transduction - drug effects</topic><topic>Signal Transduction - genetics</topic><topic>Sodium Fluoride - pharmacology</topic><topic>Wnt</topic><topic>Wnt Proteins - biosynthesis</topic><topic>Wnt Proteins - genetics</topic><topic>Wnt Signaling Pathway - drug effects</topic><topic>Wnt Signaling Pathway - genetics</topic><topic>Wnt-5a Protein</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Peng, Li</creatorcontrib><creatorcontrib>Li, Yong</creatorcontrib><creatorcontrib>Shusterman, Kate</creatorcontrib><creatorcontrib>Kuehl, Melissa</creatorcontrib><creatorcontrib>Gibson, Carolyn W.</creatorcontrib><collection>Istex</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; 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Wnt‐RhoA signaling is involved in dental enamel development. 
 Eur J Oral Sci 2011; 119 (Suppl. 1): 41–49. © 2011 Eur J Oral Sci Transgenic mice that express dominant‐negative RhoA (RhoADN) in ameloblasts have hypoplastic enamel with defects in molar cusps. β‐catenin and Wnt5a were up‐regulated in enamel organs of RhoADN transgenic mice, which indicated that both canonical and non‐canonical Wnt pathways are implicated in the process of enamel defect formation. It was hypothesized that expression of RhoADN in ameloblasts interfered with normal enamel development through the pathways that were induced by fluoride. The Wnt and RhoA pathways were further investigated in an ameloblast‐lineage cell line (ALC) by treatment with sodium fluoride (NaF). The activities of RhoA and Rho‐associated protein kinase (ROCK) II decreased significantly by 8–12 hours, similar to decreased activity in RhoADN transgenic mice. Both canonical and non‐canonical Wnt pathways were activated by treatment with NaF, which was verified by western blotting and the β‐catenin‐TCF/LEF (T cell factor lymphanoid/enhancer factor) reporter gene (TOPflash) assay. β‐catenin localization to both cytoplasm and nucleus was up‐regulated in NaF‐treated ALC, while Gsk‐3β, the negative regulator of the Wnt pathway, showed a decreased pattern of expression. The current results indicate that both Wnt and RhoA pathways are implicated in fluoride‐induced signaling transductions in the ALC as well as in the development of enamel defects in RhoADN transgenic mice.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>22243225</pmid><doi>10.1111/j.1600-0722.2011.00880.x</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Ameloblasts - drug effects
Ameloblasts - physiology
Amelogenesis - genetics
Amelogenin - biosynthesis
Amelogenin - genetics
Animals
beta Catenin - biosynthesis
beta Catenin - genetics
Cell Line
dental enamel
Dental Enamel Hypoplasia - genetics
Dentistry
Enamel Organ - drug effects
Enamel Organ - physiology
Gene Expression Regulation, Developmental
Genes, Reporter
GTP-Binding Protein Regulators - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
rho GTP-Binding Proteins - genetics
rho GTP-Binding Proteins - physiology
rho-Associated Kinases - genetics
RhoA
rhoA GTP-Binding Protein - genetics
rhoA GTP-Binding Protein - physiology
RhoADN transgenic mice
Signal Transduction - drug effects
Signal Transduction - genetics
Sodium Fluoride - pharmacology
Wnt
Wnt Proteins - biosynthesis
Wnt Proteins - genetics
Wnt Signaling Pathway - drug effects
Wnt Signaling Pathway - genetics
Wnt-5a Protein
title Wnt-RhoA signaling is involved in dental enamel development
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