help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gopalakrishnan, R.
Right arrow Articles by Franceschi, R. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gopalakrishnan, R.
Right arrow Articles by Franceschi, R. T.
Endocrinology Vol. 142, No. 10 4379-4388
Copyright © 2001 by The Endocrine Society

ARTICLES

Matrix {gamma}-Carboxyglutamic Acid Protein Is a Key Regulator of PTH-Mediated Inhibition of Mineralization in MC3T3-E1 Osteoblast-Like Cells

Rajaram Gopalakrishnan, Hongjiao Ouyang, Martha J. Somerman, Laurie K. McCauley and Renny T. Franceschi

Department of Periodontics/Prevention/Geriatrics (R.G., H.O., M.J.S., L.K.M., R.T.F.) and Department of Cariology, Restorative Sciences, and Endodontics (H.O.), School of Dentistry, and Departments of Pharmacology (M.J.S.) and Biological Chemistry (R.T.F.), School of Medicine, University of Michigan, Ann Arbor, Michigan 48109-1078

Address all correspondence and requests for reprints to: Renny T. Franceschi, Ph.D., Department of Periodontics/Prevention/Geriatrics, University of Michigan Dental School, Ann Arbor, Michigan 48109-1078. E-mail: rennyf{at}umich.edu

As part of its overall function as a major regulator of calcium homeostasis, PTH stimulates bone resorption and inhibits osteoblast-mediated biomineralization. To determine the basis for the inhibitory actions of this hormone, we compared the time course of PTH-dependent inhibition of mineralization in MC3T3-E1 osteoblast-like cells with changes in mRNA levels for several extracellular matrix proteins previously associated either with induction or inhibition of mineralization. Mineralizing activity was rapidly lost in PTH-treated cells (~30% inhibition after 3 h, 50% inhibition at 6 h). Of the proteins examined, changes in matrix {gamma}-carboxyglutamic acid protein were best correlated with PTH-dependent inhibition of mineralization. Matrix {gamma}-carboxyglutamic acid protein mRNA was rapidly induced 3 h after PTH treatment, with a 6- to 8-fold induction seen after 6 h. Local in vivo injection of PTH over the calvaria of mice also induced a 2-fold increase in matrix {gamma}-carboxyglutamic acid protein mRNA. Warfarin, an inhibitor of matrix {gamma}-carboxyglutamic acid protein {gamma}-carboxylation, reversed the effects of PTH on mineralization in MC3T3-E1 cells, whereas vitamin K enhanced PTH activity, as would be expected if a {gamma}-carboxyglutamic acid-containing protein were required for PTH activity. Levels of the other mRNAs examined were not well correlated with the observed changes in mineralization. Osteopontin, an in vitro inhibitor of mineralization, was induced approximately 4-fold 12 h after PTH addition. Bone sialoprotein mRNA, which encodes an extracellular matrix component most frequently associated with mineral induction, was inhibited by 50% after 12 h of PTH treatment. Osteocalcin mRNA, encoding the other known {gamma}-carboxyglutamic acid protein in bone, was also inhibited by PTH, but, again, with a significantly slower time course than was seen for mineral inhibition. Taken together, these results show that the rapid inhibition of osteoblast mineralization induced by in vitro PTH treatment is at least in part explained by induction of matrix {gamma}-carboxyglutamic acid protein.




This article has been cited by other articles:


Home page
 Am. J. Pathol.Home page
D. Merciris, C. Marty, C. Collet, M.-C. de Vernejoul, and V. Geoffroy
Overexpression of the Transcriptional Factor Runx2 in Osteoblasts Abolishes the Anabolic Effect of Parathyroid Hormone in Vivo
Am. J. Pathol., May 1, 2007; 170(5): 1676 - 1685.
[Abstract] [Full Text] [PDF]

Home page
 Arterioscler. Thromb. Vasc. Bio.Home page
L. J. Schurgers, K. J.F. Teunissen, M. H.J. Knapen, M. Kwaijtaal, R. van Diest, A. Appels, C. P. Reutelingsperger, J. P.M. Cleutjens, and C. Vermeer
Novel Conformation-Specific Antibodies Against Matrix {gamma}-Carboxyglutamic Acid (Gla) Protein: Undercarboxylated Matrix Gla Protein as Marker for Vascular Calcification
Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1629 - 1633.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Endocrinol.Home page
J. Lammi, J. Huppunen, and P. Aarnisalo
Regulation of the Osteopontin Gene by the Orphan Nuclear Receptor NURR1 in Osteoblasts
Mol. Endocrinol., June 1, 2004; 18(6): 1546 - 1557.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
D. Jiang, R. T. Franceschi, H. Boules, and G. Xiao
Parathyroid Hormone Induction of the Osteocalcin Gene: REQUIREMENT FOR AN OSTEOBLAST-SPECIFIC ELEMENT 1 SEQUENCE IN THE PROMOTER AND INVOLVEMENT OF MULTIPLE SIGNALING PATHWAYS
J. Biol. Chem., February 13, 2004; 279(7): 5329 - 5337.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
B. Demiralp, H.-L. Chen, A. J. Koh, E. T. Keller, and L. K. McCauley
Anabolic Actions of Parathyroid Hormone during Bone Growth Are Dependent on c-fos
Endocrinology, October 1, 2002; 143(10): 4038 - 4047.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2001 by The Endocrine Society