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    Overlapping expression of Runx1(Cbfa2) and Runx2(Cbfa1) transcription factors supports cooperative induction of skeletal development

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    Authors
    Smith, Nathan
    Dong, Yufeng
    Lian, Jane B.
    Pratap, Jitesh
    Kingsley, Paul D.
    Van Wijnen, Andre J.
    Stein, Janet L.
    Schwarz, Edward M.
    O'Keefe, Regis J.
    Stein, Gary S.
    Drissi, Hicham
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    UMass Chan Affiliations
    Department of Cell Biology
    The Center for Musculoskeletal Research
    Graduate School of Biomedical Sciences
    Document Type
    Journal Article
    Publication Date
    2004-09-25
    Keywords
    Animals; Bone Development; Calcification, Physiologic; Cartilage; Chondrogenesis; Core Binding Factor Alpha 1 Subunit; Core Binding Factor Alpha 2 Subunit; DNA-Binding Proteins; *Gene Expression Regulation, Developmental; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Mutant Strains; Proto-Oncogene Proteins; RNA, Messenger; Stem Cells; Transcription Factor AP-2; Transcription Factors
    Life Sciences
    Medicine and Health Sciences
    
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    Link to Full Text
    http://dx.doi.org/10.1002/jcp.20210
    Abstract
    Identifying the genetic pathways that regulate skeletal development is necessary to correct a variety of cartilage and bone abnormalities. The Runx family of transcription factors play a fundamental role in organ development and cell differentiation. Initial studies have shown that both Runx1 and Runx2 are expressed in pre-chondrogenic mesenchyme of the developing embryo at E12.5. Abrogation of the Runx2 gene completely inhibits bone formation yet the cartilage anlagen in these mice is fully formed. In the present study, we hypothesized that Runx1 may compensate for the lack of Runx2 in vivo to induce the early stages of skeletal formation and development. Histologic beta-gal stained sections using the Runx1(+/-)-Lac-Z mice demonstrate Runx1 promoter activity in pre-chondrocytic cell populations. In situ hybridization using Runx1 and Runx2 specific probes indicate that both factors are expressed in mesenchymal stem cell progenitors during early embryonic development. During later stages of mouse skeletal formation, Runx1 is excluded from the hypertrophic cartilage while Runx2 is present in these matured chondrocyte populations. Quantification of Runx expression by real time RT-PCR and Western blot analyses reveals that Runx1 and Runx2 are differentially modulated during embryogenesis suggesting a temporal role for each of these transcriptional regulators during skeletal formation. We provide evidence that haploinsufficiency results in normal appearing embryo skeletons of heterozygote Runx2 and Runx1 mutant mouse models; however, a delay in bone formation was identified in the calvarium. In summary, our results support a function for Runx1 and Runx2 during skeletal development with a possible role for Runx1 in mediating early events of endochondral and intramembranous bone formation, while Runx2 is a potent inducer of late stages of chondrocyte and osteoblast differentiation.
    Source
    J Cell Physiol. 2005 Apr;203(1):133-43. Link to article on publisher's site
    DOI
    10.1002/jcp.20210
    Permanent Link to this Item
    http://hdl.handle.net/20.500.14038/32570
    PubMed ID
    15389629
    Related Resources
    Link to Article in PubMed
    ae974a485f413a2113503eed53cd6c53
    10.1002/jcp.20210
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