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Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cellsBoth collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the alpha(v) integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and alpha(v) integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.
Document ID
20040088361
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
D'Alonzo, Richard C.
(Robert Wood Johnson Medical School and the Department of Cell Biology and Neuroscience, Rutgers University Piscataway, New Jersey 08854, United States)
Kowalski, Aaron J.
Denhardt, David T.
Nickols, G. Allen
Partridge, Nicola C.
Date Acquired
August 21, 2013
Publication Date
July 5, 2002
Publication Information
Publication: The Journal of biological chemistry
Volume: 277
Issue: 27
ISSN: 0021-9258
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: ESO6897
CONTRACT_GRANT: DK47420
CONTRACT_GRANT: DK48109
CONTRACT_GRANT: AR44439
Distribution Limits
Public
Copyright
Other
Keywords
NASA Discipline Musculoskeletal
Non-NASA Center

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