Abstract
CCN3/NOV activates the Notch signal through the carboxyl terminal cysteine-rich (CT) domain. CCN3 transfection to Kusa-A1 inhibited osteogenic differentiation and cell proliferation, which is accompanied by upregulation of Hes/Hey, Notch downstream targets, and p21, a CDK inhibitor. Upregulation of Hes/Hey and p21 was abrogated by the deletion of CT domain. Anti-proliferative activity of CCN3 was also abrogated by CT domain deletion whereas anti-osteogenic activity was not completely abrogated. We found that CT domain-deleted CCN3 still possesses antagonistic effect on BMP-2. These results suggest that CCN3 employs Notch and BMP pathways in anti-osteogenic activity while it inhibits cell proliferation uniquely by Notch/p21 pathway.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Differentiation
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Cell Line
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Cell Proliferation
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Connective Tissue Growth Factor
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Humans
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Immediate-Early Proteins / chemistry
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Immediate-Early Proteins / metabolism*
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Intercellular Signaling Peptides and Proteins / chemistry
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Intercellular Signaling Peptides and Proteins / metabolism*
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Mesenchymal Stem Cells / cytology*
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Mesenchymal Stem Cells / physiology*
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Nephroblastoma Overexpressed Protein
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Osteoblasts / cytology*
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Osteoblasts / physiology*
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Osteogenesis / physiology*
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Protein Structure, Tertiary
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Structure-Activity Relationship
Substances
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CCN2 protein, human
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CCN3 protein, human
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Immediate-Early Proteins
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Intercellular Signaling Peptides and Proteins
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Nephroblastoma Overexpressed Protein
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Connective Tissue Growth Factor