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Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells.

Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Research Abstract Details 

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  • Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Abstract Text:

    guozhi xiaoGuozhi Xiao,rajaram gopalakrishnanRajaram Gopalakrishnan,di jiangDi Jiang,elizabeth reithElizabeth Reith,m douglas bensonM Douglas Benson,renny t franceschiRenny T Franceschi,

    Osteoblasts secrete a complex extracellular matrix (ECM) containing collagenous and noncollagenous proteins, bone morphogenetic proteins (BMPs), and growth factors. Osteoblast-specific gene expression requires ascorbic acid (AA)-dependent assembly of a collagenous ECM. Matrix responsiveness requires an alpha2beta1 integrin-collagen interaction and mitogen-activated protein kinase (MAPK) activity, which phosphorylates and activates the osteoblast-specific transcription factor Cbfa1. This study examines interactions between this integrin/MAPK-mediated pathway and signals initiated by BMPs contained in the osteoblast matrix. MC3T3-E1 cells were shown to constitutively express BMP-2, BMP-4, and BMP-7. Noggin, a specific BMP inhibitor, reversibly blocked AA-induced gene expression, indicating that BMP production by MC3T3-E1 cells was necessary for differentiation. The ability of exogenously added BMP-2, BMP-4, or BMP-7 to stimulate osteocalcin (OCN) and bone sialoprotein (BSP) mRNAs or OCN promoter activity was synergistically increased in cells that were actively synthesizing an ECM (i.e., were grown in the presence of AA). A minimum of 4 days of ECM accumulation was required for this synergistic response to be observed. Neither BMP-7, AA, nor a combination of these two treatments had major effects on Cbfa1 messenger RNA (mRNA) or protein levels, as would be expected if regulation was mainly at the posttranscriptional level. U0126, a specific inhibitor of MAPK/extracellular signal-regulated kinase (MEK), blocked AA- or BMP-7/AA-dependent gene expression in a time- and dose-dependent manner that was closely correlated with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation. This work establishes that autocrine BMP production as well as integrin-mediated cell-collagen interactions are both required for osteoblast differentiation, and both these pathways require MAP kinase activity.

    Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Publishing Authors By Initials

    g xiaoG Xiao,r gopalakrishnanR Gopalakrishnan,d jiangD Jiang,e reithE Reith,md bensonMD Benson,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:

    Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Journal Published:

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

    Journal: Journal of bone and mineral research : the officia

    VOLUME: 17

    Page Numbers: 101-10

    Journal Abbreviation: J. Bone Miner. Res.

    ISSN: 0884-0431

    DAY: 19

    MONTH: Jan

    YEAR: 2002

    Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Information

    Number of References:

    LANGUAGE: eng

    NlmUniqueID: 8610640

    Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Keywords Mesh Terms:

    KEYWORDS: Transforming Growth Factor beta

    MESH TERMS: genetics

    Chemical & Substance for Abstract: Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells. Information

    Substance Name: Mitogen-Activated Protein Kinases

    Registry Number: EC 2.7.1.37

    Grant and Affiliation Information for Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells.

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

    Country: United States

    United States Research PublicationUnited States Research Publication

    AGENCY: United States NIDCR

    GRANT: DE 11723

    ACRONYM: DE

    MEDLINETA: J Bone Miner Res

    REFSOURCE:

    DATABASENAME:

    ACCESSION NUMBER:

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    Bone morphogenetic proteins, extracellular matrix, and mitogen-activated protein kinase signaling pathways are required for osteoblast-specific gene expression and differentiation in MC3T3-E1 cells Related Publications

     

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