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In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation.

In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Research Abstract Details 

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  • In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Abstract Text:

    shuying yangShuying Yang,daoyan weiDaoyan Wei,dian wangDian Wang,mattabhorn phimphilaiMattabhorn Phimphilai,paul h krebsbachPaul H Krebsbach,renny t franceschiRenny T Franceschi,

    Bone regeneration requires interactions between a number of factors including bone morphogenetic proteins (BMPs), growth factors, and transcriptional regulators such as Runx2/Cbfal (Runx2). Because each component may provide a unique contribution to the overall osteogenic response, we hypothesized that bone formation may be enhanced by using combinations of complimentary factors. As an initial test of this concept, interactions between BMP2 and Runx2 were examined using adenovirus-based expression vectors (AdCMV-Runx2, AdCMV-BMP2) in the pluripotent C3H10T1/2 cell line. Cells transduced with AdCMV-Runx2 strongly expressed osteoblast markers, such as alkaline phosphatase and osteocalcin, but formed only a weakly mineralized extracellular matrix in vitro, whereas cells transduced with AdCMV-BMP2 exhibited higher levels of mineralization, but only expressed low levels of Runx2 and osteocalcin mRNA. Significantly, when cells were transduced with optimal titers of both viruses, osteoblast differentiation was stimulated to levels that were 10-fold greater than those seen with either AdCMV-Runx2 or AdCMV-BMP2 alone. To measure in vivo osteogenic activity, virally transduced cells were subcutaneously implanted into immunodeficient mice. Cells transduced with control virus produced only fibrous tissue while those with AdCMV-Runx2 produced limited amounts of both cartilage and bone. In contrast, cells transduced with either AdCMV-BMP2 alone or AdCMV-BMP2 plus AdCMV-Cbfal generated large ossicles containing cartilage, bone, and a marrow cavity. However, ossification in the AdCMV-BMP2 plus AdCMV-Cbfal group was more extensive in that both mineral content and fractional bone area were greater than that seen in the AdCMV-BMP2 group. Thus, the increased osteoblast differentiation observed with combined adenovirus treatment in vitro is also manifested by increased bone formation in vivo. These results suggest that Runx2 and BMP2 have distinct, but complementary, roles in osteogenesis and that their combined actions may be necessary for optimal bone formation.

    In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Publishing Authors By Initials

    s yangS Yang,d weiD Wei,d wangD Wang,m phimphilaiM Phimphilai,ph krebsbachPH Krebsbach,rt franceschiRT Franceschi,

    For similar peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research abstracts see: peptides: intercellular signaling peptides and proteins: cytokines: transforming growth factor beta research

    PUBMED ID PMID:

    MEDLINE DATE:

    In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Journal Published:

    PUBLICATION TYPE: Research Support, U.S. Gov't,

    Journal: Journal of bone and mineral research : the officia

    VOLUME: 18

    Page Numbers: 705-15

    Journal Abbreviation: J. Bone Miner. Res.

    ISSN: 0884-0431

    DAY: 19

    MONTH: Apr

    YEAR: 2003

    In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8610640

    In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Keywords Mesh Terms:

    KEYWORDS: Transforming Growth Factor beta

    MESH TERMS: metabolism

    Chemical & Substance for Abstract: In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation. Information

    Substance Name: bone morphogenetic protein 2

    Registry Number: 0

    Grant and Affiliation Information for In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation.

    AFFILIATION: Department of Periodontics, Prevention, and Geriatrics, School of Dentistry, University of Michigan, Ann Arbor, Michigan 48109-1078, USA.

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDCR

    GRANT: DE13835

    ACRONYM: DE

    MEDLINETA: J Bone Miner Res

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

    Number Hits: 0

    In vitro and in vivo synergistic interactions between the Runx2/Cbfa1 transcription factor and bone morphogenetic protein-2 in stimulating osteoblast differentiation Related Publications

     

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