|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 50, 48868-48875, December 13, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Parathyroid hormone (PTH) stimulates osteoclast
formation by binding to its receptor on stromal/osteoblastic cells and
stimulating the production of receptor activator of NF
Parathyroid Hormone Stimulates Receptor Activator of NF
B
Ligand and Inhibits Osteoprotegerin Expression via Protein Kinase A
Activation of cAMP-response Element-binding Protein*
,§,§, and¶
Division of Endocrinology & Metabolism,
Center for Osteoporosis & Metabolic Bone Diseases and the
§ Central Arkansas Veterans Healthcare System, University of
Arkansas for Medical Sciences, Little Rock, Arkansas 72205
B ligand
(RANKL) and inhibiting the expression of osteoprotegerin (OPG).
However, the mechanisms through which PTH regulates these genes remain
unknown. Here we report that PTH stimulated RANKL gene transcription
and increased RANKL mRNA stability in murine stromal/osteoblastic cells stably expressing human PTH/PTH-related protein receptor 1. PTH also potently suppressed OPG mRNA in these cells.
Cycloheximide did not block the effects of PTH on RANKL but did inhibit
the suppression of OPG mRNA. Activation of protein kinase A (PKA) was necessary and sufficient for the effect of PTH on both genes. Conditional expression of a dominant-negative form of the transcription factor CREB, but not c-fos or Runx2, significantly
reduced PTH stimulation of RANKL. CREB activity was also required for
full stimulation of RANKL by oncostatin M or 1,25-dihydroxyvitamin D3. Dominant-negative forms of CREB and c-fos
reduced the suppression of OPG by PTH. These results demonstrate that
PTH directly stimulates RANKL expression via a PKA-CREB pathway and
that CREB may be a central regulator of RANKL expression. Furthermore,
they suggest that PTH suppression of OPG involves CREB and
c-fos.
*
This work was supported by National Institutes of Health
Grant R01-AR45241 and by a University of Arkansas for Medical Sciences institutional grant (to C. A. O.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Galli, Q. Fu, W. Wang, B. R. Olsen, S. C. Manolagas, R. L. Jilka, and C. A. O'Brien Commitment to the Osteoblast Lineage Is Not Required for RANKL Gene Expression J. Biol. Chem., May 8, 2009; 284(19): 12654 - 12662. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Rashid, E. Plotkin, O. Klein, J. Green, J. Bernheim, and S. Benchetrit Parathyroid hormone decreases endothelial osteoprotegerin secretion: role of protein kinase A and C Am J Physiol Renal Physiol, January 1, 2009; 296(1): F60 - F66. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Clauss, M.-C. Maniere, F. Obry, E. Waltmann, S. Hadj-Rabia, C. Bodemer, Y. Alembik, H. Lesot, and M. Schmittbuhl Dento-Craniofacial Phenotypes and underlying Molecular Mechanisms in Hypohidrotic Ectodermal Dysplasia (HED): a Review Journal of Dental Research, December 1, 2008; 87(12): 1089 - 1099. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. Kearns, S. Khosla, and P. J. Kostenuik Receptor Activator of Nuclear Factor {kappa}B Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease Endocr. Rev., April 1, 2008; 29(2): 155 - 192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. J. Raggatt, L. Qin, J. Tamasi, S. C. Jefcoat Jr., E. Shimizu, N. Selvamurugan, F. Y. Liew, L. Bevelock, J. H. M. Feyen, and N. C. Partridge Interleukin-18 Is Regulated by Parathyroid Hormone and Is Required for Its Bone Anabolic Actions J. Biol. Chem., March 14, 2008; 283(11): 6790 - 6798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. A. Nakchbandi, R. Lang, B. Kinder, and K. L. Insogna The Role of the Receptor Activator of Nuclear Factor-{kappa}B Ligand/Osteoprotegerin Cytokine System in Primary Hyperparathyroidism J. Clin. Endocrinol. Metab., March 1, 2008; 93(3): 967 - 973. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Galli, L. A. Zella, J. A. Fretz, Q. Fu, J. W. Pike, R. S. Weinstein, S. C. Manolagas, and C. A. O'Brien Targeted Deletion of a Distant Transcriptional Enhancer of the Receptor Activator of Nuclear Factor-{kappa}B Ligand Gene Reduces Bone Remodeling and Increases Bone Mass Endocrinology, January 1, 2008; 149(1): 146 - 153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Ono, K. Nakashima, E. Schipani, T. Hayata, Y. Ezura, K. Soma, H. M. Kronenberg, and M. Noda Constitutively Active Parathyroid Hormone Receptor Signaling in Cells in Osteoblastic Lineage Suppresses Mechanical Unloading-induced Bone Resorption J. Biol. Chem., August 31, 2007; 282(35): 25509 - 25516. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Fionda, F. Nappi, M. Piccoli, L. Frati, A. Santoni, and M. Cippitelli 15-Deoxy-{Delta}12,14-Prostaglandin J2 Negatively Regulates rankl Gene Expression in Activated T Lymphocytes: Role of NF-{kappa}B and Early Growth Response Transcription Factors J. Immunol., April 1, 2007; 178(7): 4039 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kousteni, M. Almeida, L. Han, T. Bellido, R. L. Jilka, and S. C. Manolagas Induction of Osteoblast Differentiation by Selective Activation of Kinase-Mediated Actions of the Estrogen Receptor Mol. Cell. Biol., February 15, 2007; 27(4): 1516 - 1530. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kim, M. Yamazaki, N. K. Shevde, and J. W. Pike Transcriptional Control of Receptor Activator of Nuclear Factor-{kappa}B Ligand by the Protein Kinase A Activator Forskolin and the Transmembrane Glycoprotein 130-Activating Cytokine, Oncostatin M, Is Exerted through Multiple Distal Enhancers Mol. Endocrinol., January 1, 2007; 21(1): 197 - 214. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Fu, S. C. Manolagas, and C. A. O'Brien Parathyroid Hormone Controls Receptor Activator of NF-{kappa}B Ligand Gene Expression via a Distant Transcriptional Enhancer. Mol. Cell. Biol., September 1, 2006; 26(17): 6453 - 6468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kim, M. Yamazaki, L. A. Zella, N. K. Shevde, and J. W. Pike Activation of Receptor Activator of NF-{kappa}B Ligand Gene Expression by 1,25-Dihydroxyvitamin D3 Is Mediated through Multiple Long-Range Enhancers. Mol. Cell. Biol., September 1, 2006; 26(17): 6469 - 6486. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Villa, E. Mrak, A. Rubinacci, F. Ravasi, and F. Guidobono CGRP inhibits osteoprotegerin production in human osteoblast-like cells via cAMP/PKA-dependent pathway Am J Physiol Cell Physiol, September 1, 2006; 291(3): C529 - C537. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Bergh, Y. Shao, E. Puente, R. L. Duncan, and M. C. Farach-Carson Osteoblast Ca2+ permeability and voltage-sensitive Ca2+ channel expression is temporally regulated by 1,25-dihydroxyvitamin D3 Am J Physiol Cell Physiol, March 1, 2006; 290(3): C822 - C831. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. O'Brien, R. L. Jilka, Q. Fu, S. Stewart, R. S. Weinstein, and S. C. Manolagas IL-6 is not required for parathyroid hormone stimulation of RANKL expression, osteoclast formation, and bone loss in mice Am J Physiol Endocrinol Metab, November 1, 2005; 289(5): E784 - E793. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. V. Komarova Mathematical Model of Paracrine Interactions between Osteoclasts and Osteoblasts Predicts Anabolic Action of Parathyroid Hormone on Bone Endocrinology, August 1, 2005; 146(8): 3589 - 3595. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X.-c. Bai, D. Lu, A.-l. Liu, Z.-m. Zhang, X.-m. Li, Z.-p. Zou, W.-s. Zeng, B.-l. Cheng, and S.-q. Luo Reactive Oxygen Species Stimulates Receptor Activator of NF-{kappa}B Ligand Expression in Osteoblast J. Biol. Chem., April 29, 2005; 280(17): 17497 - 17506. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. A. Ali, R. S. Weinstein, S. A. Stewart, A. M. Parfitt, S. C. Manolagas, and R. L. Jilka Rosiglitazone Causes Bone Loss in Mice by Suppressing Osteoblast Differentiation and Bone Formation Endocrinology, March 1, 2005; 146(3): 1226 - 1235. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Murray, L. G. Rao, P. Divieti, and F. R. Bringhurst Parathyroid Hormone Secretion and Action: Evidence for Discrete Receptors for the Carboxyl-Terminal Region and Related Biological Actions of Carboxyl- Terminal Ligands Endocr. Rev., February 1, 2005; 26(1): 78 - 113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. C. Ozkurt, F. Q. Pirih, and S. Tetradis Parathyroid Hormone Induces E4bp4 Messenger Ribonucleic Acid Expression Primarily through Cyclic Adenosine 3',5'-Monophosphate Signaling in Osteoblasts Endocrinology, August 1, 2004; 145(8): 3696 - 3703. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Buxton, W. Yao, and N. E. Lane Changes in Serum Receptor Activator of Nuclear Factor-{kappa}B Ligand, Osteoprotegerin, and Interleukin-6 Levels in Patients with Glucocorticoid-Induced Osteoporosis Treated with Human Parathyroid Hormone (1-34) J. Clin. Endocrinol. Metab., July 1, 2004; 89(7): 3332 - 3336. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U. H. Lerner NEW MOLECULES IN THE TUMOR NECROSIS FACTOR LIGAND AND RECEPTOR SUPERFAMILIES WITH IMPORTANCE FOR PHYSIOLOGICAL AND PATHOLOGICAL BONE RESORPTION Critical Reviews in Oral Biology & Medicine, March 1, 2004; 15(2): 64 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Suda, N. Udagawa, N. Sato, M. Takami, K. Itoh, J.-T. Woo, N. Takahashi, and K. Nagai Suppression of Osteoprotegerin Expression by Prostaglandin E2 Is Crucially Involved in Lipopolysaccharide-Induced Osteoclast Formation J. Immunol., February 15, 2004; 172(4): 2504 - 2510. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Buttitta, R. Mo, C.-C. Hui, and C.-M. Fan Interplays of Gli2 and Gli3 and their requirement in mediating Shh-dependent sclerotome induction Development, December 22, 2003; 130(25): 6233 - 6243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Bellido, A. A. Ali, L. I. Plotkin, Q. Fu, I. Gubrij, P. K. Roberson, R. S. Weinstein, C. A. O'Brien, S. C. Manolagas, and R. L. Jilka Proteasomal Degradation of Runx2 Shortens Parathyroid Hormone-induced Anti-apoptotic Signaling in Osteoblasts: A PUTATIVE EXPLANATION FOR WHY INTERMITTENT ADMINISTRATION IS NEEDED FOR BONE ANABOLISM J. Biol. Chem., December 12, 2003; 278(50): 50259 - 50272. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |