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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
5
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pubmed:dateCreated |
2008-5-14
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pubmed:abstractText |
Hedgehog (Hh)-Patched1 (Ptch1) signaling plays essential roles in various developmental processes, but little is known about its role in postnatal homeostasis. Here, we demonstrate regulation of postnatal bone homeostasis by Hh-Ptch1 signaling. Ptch1-deficient (Ptch1+/-) mice and patients with nevoid basal cell carcinoma syndrome showed high bone mass in adults. In culture, Ptch1+/- cells showed accelerated osteoblast differentiation, enhanced responsiveness to the runt-related transcription factor 2 (Runx2), and reduced generation of the repressor form of Gli3 (Gli3rep). Gli3rep inhibited DNA binding by Runx2 in vitro, suggesting a mechanism that could contribute to the bone phenotypes seen in the Ptch1 heterozygotes. Moreover, systemic administration of the Hh signaling inhibitor cyclopamine decreased bone mass in adult mice. These data provide evidence that Hh-Ptch1 signaling plays a crucial role in postnatal bone homeostasis and point to Hh-Ptch1 signaling as a potential molecular target for the treatment of osteoporosis.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Core Binding Factor Alpha 1 Subunit,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/Gli3 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Hedgehog Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Kruppel-Like Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/patched receptors
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1878-1551
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pubmed:author |
pubmed-author:ChungUng-IlUI,
pubmed-author:FujiiKatsunoriK,
pubmed-author:IkedaToshiyukiT,
pubmed-author:KawaguchiHiroshiH,
pubmed-author:KawamuraNaohiroN,
pubmed-author:KugimiyaFumitakaF,
pubmed-author:KuramochiAkiraA,
pubmed-author:MiyajimaTsuyoshiT,
pubmed-author:MiyashitaToshiyukiT,
pubmed-author:NakamuraKozoK,
pubmed-author:OdaHiromiH,
pubmed-author:OgasawaraToruT,
pubmed-author:OhbaShinsukeS,
pubmed-author:SaitoTakuT,
pubmed-author:TakatoTsuyoshiT
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pubmed:issnType |
Electronic
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pubmed:volume |
14
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
689-99
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pubmed:dateRevised |
2009-5-22
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pubmed:meshHeading |
pubmed-meshheading:18477452-Animals,
pubmed-meshheading:18477452-Bone and Bones,
pubmed-meshheading:18477452-Cell Differentiation,
pubmed-meshheading:18477452-Cells, Cultured,
pubmed-meshheading:18477452-Core Binding Factor Alpha 1 Subunit,
pubmed-meshheading:18477452-DNA,
pubmed-meshheading:18477452-Gene Expression Regulation,
pubmed-meshheading:18477452-Haploidy,
pubmed-meshheading:18477452-Hedgehog Proteins,
pubmed-meshheading:18477452-Humans,
pubmed-meshheading:18477452-Kruppel-Like Transcription Factors,
pubmed-meshheading:18477452-Mice,
pubmed-meshheading:18477452-Nerve Tissue Proteins,
pubmed-meshheading:18477452-Organ Size,
pubmed-meshheading:18477452-Osteoblasts,
pubmed-meshheading:18477452-Protein Binding,
pubmed-meshheading:18477452-Receptors, Cell Surface,
pubmed-meshheading:18477452-Repressor Proteins,
pubmed-meshheading:18477452-Signal Transduction,
pubmed-meshheading:18477452-Stem Cells,
pubmed-meshheading:18477452-Transcription, Genetic
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pubmed:year |
2008
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pubmed:articleTitle |
Patched1 haploinsufficiency increases adult bone mass and modulates Gli3 repressor activity.
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pubmed:affiliation |
Department of Sensory and Motor System Medicine, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-8655, Japan. shin-o@umin.ac.jp
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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