title: Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: a mouse model.
abstract: Endochondral bone formation begins with the development of a cartilage intermediate that is subsequently replaced by calcified bone. The mechanisms occurring during early chondrogenesis that control both mesenchymal cell differentiation into chondrocytes and cell proliferation are not clearly understood in vertebrates. Indian hedgehog (Ihh), one of the hedgehog signaling molecules, is known to control both the hypertrophy of chondrocytes and bone replacement; these processes are particularly important in postnatal endochondral bone formation rather than in early chondrogenesis. In this study, we utilized the maternal transfer of 5E1 to E12.5 in mouse embryos, a process that leads to an attenuation of Ihh activity. As a result, mouse limb bud chondrogenesis was inhibited, and an exogenous recombinant IHH protein enhanced the proliferation and differentiation of mesenchymal cells. Analysis of the genetic relationships in the limb buds suggested a more extensive role for Ihh and Runx genes in early chondrogenesis. The transfer of 5E1 decreased the expression of Runx2 and Runx3, whereas an exogenous recombinant IHH protein increased Runx2 and Runx3 expression. Moreover, a transcription factor Gli1 in hedgehog pathway enhances the direct induction of both Runx2 and Runx3 transcription. These findings suggested that Ihh signaling plays an important role in chondrocyte proliferation and differentiation via interactions with Runx2 and Runx3.
authors: Division in Anatomy and Developmental Biology, Department of Oral Biology, Research Center for Orofacial Hard Tissue Regeneration, Brain Korea 21 Project, Oral Science Research Center, College of Dentistry, Yonsei University, Seoul, Korea. blueleah@yuhs.ac
authors: Eun-Jung
authors: EJ
authors: Kim
authors: Sung-Won
authors: SW
authors: Cho
authors: Jeong-Oh
authors: JO
authors: Shin
authors: Min-Jung
authors: MJ
authors: Lee
authors: Kye-Seong
authors: KS
authors: Kim
authors: Han-Sung
authors: HS
authors: Jung
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D020219:Chondrogenesis / Q000502:physiology*; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D050677:Core Binding Factor Alpha 3 Subunit / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D053823:Hedgehog Proteins / Q000378:metabolism*; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008156:Luciferases; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D046228:Microarray Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D055114:X-Ray Microtomography; D000071676:Zinc Finger Protein GLI1
chemical_list: D000911:Antibodies, Monoclonal; D050659:Core Binding Factor Alpha 1 Subunit; D050677:Core Binding Factor Alpha 3 Subunit; D017931:DNA Primers; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; C493716:Runx2 protein, mouse; C493730:Runx3 protein, mouse; D000071676:Zinc Finger Protein GLI1; C514061:ihh protein, mouse; D008156:Luciferases
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