| http://purl.uniprot.org/citations/29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29735531 | http://www.w3.org/2000/01/rdf-schema#comment | "Chondrocyte hypertrophy is the terminal step in chondrocyte differentiation and is crucial for endochondral bone formation. How signaling pathways regulate chondrocyte hypertrophic differentiation remains incompletely understood. In this study, using a Tbx18:Cre (Tbx18Cre/+) gene-deletion approach, we selectively deleted the gene for the signaling protein SMAD family member 4 (Smad4f/f ) in the limbs of mice. We found that the Smad4-deficient mice develop a prominent shortened limb, with decreased expression of chondrocyte differentiation markers, including Col2a1 and Acan, in the humerus at mid-to-late gestation. The most striking defects in these mice were the absence of stylopod elements and failure of chondrocyte hypertrophy in the humerus. Moreover, expression levels of the chondrocyte hypertrophy-related markers Col10a1 and Panx3 were significantly decreased. Of note, we also observed that the expression of runt-related transcription factor 2 (Runx2), a critical mediator of chondrocyte hypertrophy, was also down-regulated in Smad4-deficient limbs. To determine how the skeletal defects arose in the mouse mutants, we performed RNA-Seq with ChIP-Seq analyses and found that Smad4 directly binds to regulatory elements in the Runx2 promoter. Our results suggest a new mechanism whereby Smad4 controls chondrocyte hypertrophy by up-regulating Runx2 expression during skeletal development. The regulatory mechanism involving Smad4-mediated Runx2 activation uncovered here provides critical insights into bone development and pathogenesis of chondrodysplasia."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.org/dc/terms/identifier | "doi:10.1074/jbc.ra118.001825"xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Cai X."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Li J."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Hu J."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Zhang W."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Zhang L."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Yan J."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Wei C."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Cai C.L."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/author | "Sultana N."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/date | "2018"xsd:gYear |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/name | "J Biol Chem"xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/pages | "9162-9175"xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/title | "Smad4 deficiency impairs chondrocyte hypertrophy via the Runx2 transcription factor in mouse skeletal development."xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://purl.uniprot.org/core/volume | "293"xsd:string |
| http://purl.uniprot.org/citations/29735531 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/29735531 |
| http://purl.uniprot.org/citations/29735531 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/29735531 |
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| http://purl.uniprot.org/uniprot/#_E0CZ12-mappedCitation-29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29735531 |
| http://purl.uniprot.org/uniprot/#_E0CZC6-mappedCitation-29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29735531 |
| http://purl.uniprot.org/uniprot/#_A0A0U1RQ88-mappedCitation-29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29735531 |
| http://purl.uniprot.org/uniprot/#_F7CN98-mappedCitation-29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29735531 |
| http://purl.uniprot.org/uniprot/#_A6H5Z1-mappedCitation-29735531 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/29735531 |