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 Tai, H.
Right arrow Articles by Suda, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Tai, H.
Right arrow Articles by Suda, T.
Right arrowPubmed/NCBI databases
*Gene*GEO Profiles
*HomoloGene*UniGene
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*INDOMETHACIN
Endocrinology Vol. 138, No. 6 2372-2379
Copyright © 1997 by The Endocrine Society

ARTICLES

Transcriptional Induction of Cyclooxygenase-2 in Osteoblasts Is Involved in Interleukin-6-Induced Osteoclast Formation1

Hitoshi Tai, Chisato Miyaura, Carol C. Pilbeam, Tatsuya Tamura, Yoshiyuki Ohsugi, Yasuo Koishihara, Noboru Kubodera, Hiroshi Kawaguchi, Lawrence G. Raisz and Tatsuo Suda

Department of Biochemistry, School of Dentistry, Showa University (C.M., T.T., T.S.), 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142; and Fuji Gotemba Research Laboratories, Chugai Pharmaceutical Co., Ltd. (H.T., T.T., Y.O., Y.K., N.K.), Shizuoka 412, Japan; and the Division of Endocrinology and Metabolism, Department of Medicine, University of Connecticut Health Center (C.C.P., H.K., L.G.R.), Farmington, Connecticut 06030

Address all correspondence and requests for reprints to: Dr. Tatsuo Suda, Department of Biochemistry, School of Dentistry, Showa University, 1–5-8 Hatanodai, Shinagawa-ku, Tokyo 142, Japan.

Interleukin-6 (IL-6) induces osteoclast-like cell (osteoclast) formation in a dose-dependent fashion in cocultures of mouse bone marrow cells and osteoblastic cells when soluble IL-6 receptor (sIL-6R) is present. Simultaneous treatment with submaximal doses of IL-1{alpha} and IL-6 with sIL-6R caused marked induction of osteoclast formation and PGE2 synthesis. These effects were suppressed by adding neutralizing antibodies against IL-1{alpha} or IL-6R and were totally abolished by adding nonsteroidal antiinflammatory drugs, such as indomethacin and a selective cyclooxygenase-2 (COX-2) inhibitor (NS398). In mouse osteoblastic cells, both IL-1{alpha} and IL-6 with sIL-6R markedly induced messenger RNA expression of COX-2, but not COX-1, as determined by Northern blot analysis, and luciferase activity in cells stably transfected with a COX-2 promoter-luciferase fusion construct. IL-6 and sIL-6R, when added separately, did not stimulate COX-2 messenger RNA expression. Simultaneous addition of IL-1{alpha} and IL-6 with sIL-6R to osteoblast cultures cooperatively induced transcription of COX-2, which was associated with a marked increase in COX activity measured by the conversion of arachidonic acid into PGE2. The increased PGE2 synthesis by osteoblasts may play an important role in osteoclastogenesis induced by submaximal doses of IL-1 and IL-6.




This article has been cited by other articles:


Home page
 Toxicol PatholHome page
Z. A. Radi
Pathophysiology of Cyclooxygenase Inhibition in Animal Models
Toxicol Pathol, January 1, 2009; 37(1): 34 - 46.
[Abstract] [Full Text] [PDF]

Home page
 Infect. Immun.Home page
S. N. Somayaji, S. Ritchie, M. Sahraei, I. Marriott, and M. C. Hudson
Staphylococcus aureus Induces Expression of Receptor Activator of NF-{kappa}B Ligand and Prostaglandin E2 in Infected Murine Osteoblasts
Infect. Immun., November 1, 2008; 76(11): 5120 - 5126.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
S. Ramanadham, K. E. Yarasheski, M. J. Silva, M. Wohltmann, D. V. Novack, B. Christiansen, X. Tu, S. Zhang, X. Lei, and J. Turk
Age-Related Changes in Bone Morphology Are Accelerated in Group VIA Phospholipase A2 (iPLA2{beta})-Null Mice
Am. J. Pathol., April 1, 2008; 172(4): 868 - 881.
[Abstract] [Full Text] [PDF]

Home page
 JDRHome page
S. Ogata, Y. Kubota, T. Yamashiro, H. Takeuchi, T. Ninomiya, Y. Suyama, and K. Shirasuna
Signaling Pathways Regulating IL-1{alpha}-induced COX-2 Expression
Journal of Dental Research, February 1, 2007; 86(2): 186 - 191.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Inada, C. Matsumoto, S. Uematsu, S. Akira, and C. Miyaura
Membrane-Bound Prostaglandin E Synthase-1-Mediated Prostaglandin E2 Production by Osteoblast Plays a Critical Role in Lipopolysaccharide-Induced Bone Loss Associated with Inflammation
J. Immunol., August 1, 2006; 177(3): 1879 - 1885.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
B. Hoang, L. Zhu, Y. Shi, P. Frost, H. Yan, S. Sharma, S. Sharma, L. Goodglick, S. Dubinett, and A. Lichtenstein
Oncogenic RAS mutations in myeloma cells selectively induce cox-2 expression, which participates in enhanced adhesion to fibronectin and chemoresistance
Blood, June 1, 2006; 107(11): 4484 - 4490.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Y. Han, N. K. Lee, K. H. Kim, I. W. Jang, M. Yim, J. H. Kim, W. J. Lee, and S. Y. Lee
Transcriptional induction of cyclooxygenase-2 in osteoclast precursors is involved in RANKL-induced osteoclastogenesis
Blood, August 15, 2005; 106(4): 1240 - 1245.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
M. Xu, S. Choudhary, D. Goltzman, F. Ledgard, D. Adams, G. Gronowicz, B. Koczon-Jaremko, L. Raisz, and C. Pilbeam
Do Cyclooxygenase-2 Knockout Mice Have Primary Hyperparathyroidism?
Endocrinology, April 1, 2005; 146(4): 1843 - 1853.
[Abstract] [Full Text] [PDF]

Home page
 JEMHome page
C. Miyaura, M. Inada, C. Matsumoto, T. Ohshiba, N. Uozumi, T. Shimizu, and A. Ito
An Essential Role of Cytosolic Phospholipase A2{alpha} in Prostaglandin E2-mediated Bone Resorption Associated with Inflammation
J. Exp. Med., May 19, 2003; 197(10): 1303 - 1310.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H.-F. Cheng and R. C. Harris
Cyclooxygenase-2 Expression in Cultured Cortical Thick Ascending Limb of Henle Increases in Response to Decreased Extracellular Ionic Content by Both Transcriptional and Post-transcriptional Mechanisms. ROLE OF p38-MEDIATED PATHWAYS
J. Biol. Chem., November 15, 2002; 277(47): 45638 - 45643.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. Palmqvist, E. Persson, H. H. Conaway, and U. H. Lerner
IL-6, Leukemia Inhibitory Factor, and Oncostatin M Stimulate Bone Resorption and Regulate the Expression of Receptor Activator of NF-{kappa}B Ligand, Osteoprotegerin, and Receptor Activator of NF-{kappa}B in Mouse Calvariae
J. Immunol., September 15, 2002; 169(6): 3353 - 3362.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
A. A. Ragab, J. L. Nalepka, Y. Bi, and E. M. Greenfield
Cytokines synergistically induce osteoclast differentiation: support by immortalized or normal calvarial cells
Am J Physiol Cell Physiol, September 1, 2002; 283(3): C679 - C687.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
T. Lahiri, J. D. Laporte, P. E. Moore, R. A. Panettieri Jr., and S. A. Shore
Interleukin-6 family cytokines: signaling and effects in human airway smooth muscle cells
Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1225 - L1232.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
X. Li, Y. Okada, C. C. Pilbeam, J. A. Lorenzo, C. R. J. Kennedy, R. M. Breyer, and L. G. Raisz
Knockout of the Murine Prostaglandin EP2 Receptor Impairs Osteoclastogenesis in Vitro
Endocrinology, June 1, 2000; 141(6): 2054 - 2061.
[Abstract] [Full Text] [PDF]

Home page
 Arch Intern MedHome page
P. E. Lipsky, P. Brooks, L. J. Crofford, R. DuBois, D. Graham, L. S. Simon, L. B. A. van de Putte, and S. B. Abramson
Unresolved Issues in the Role of Cyclooxygenase-2 in Normal Physiologic Processes and Disease
Arch Intern Med, April 10, 2000; 160(7): 913 - 920.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
T. Suzawa, C. Miyaura, M. Inada, T. Maruyama, Y. Sugimoto, F. Ushikubi, A. Ichikawa, S. Narumiya, and T. Suda
The Role of Prostaglandin E Receptor Subtypes (EP1, EP2, EP3, and EP4) in Bone Resorption: An Analysis Using Specific Agonists for the Respective EPs
Endocrinology, April 1, 2000; 141(4): 1554 - 1559.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
S. Narumiya, Y. Sugimoto, and F. Ushikubi
Prostanoid Receptors: Structures, Properties, and Functions
Physiol Rev, October 1, 1999; 79(4): 1193 - 1226.
[Abstract] [Full Text] [PDF]

Home page
 NEJMHome page
C. Gabay and I. Kushner
Acute-Phase Proteins and Other Systemic Responses to Inflammation
N. Engl. J. Med., February 11, 1999; 340(6): 448 - 454.
[Full Text] [PDF]

Home page
 FASEB J.Home page
R. N. Dubois, S. B. Abramson, L. Crofford, R. A. Gupta, L. S. Simon, L. B. A. van de putte, and P. E. Lipsky
Cyclooxygenase in biology and disease
FASEB J, September 1, 1998; 12(12): 1063 - 1073.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
C. Miyaura, M. Inada, T. Suzawa, Y. Sugimoto, F. Ushikubi, A. Ichikawa, S. Narumiya, and T. Suda
Impaired Bone Resorption to Prostaglandin E2 in Prostaglandin E Receptor EP4-knockout Mice
J. Biol. Chem., June 23, 2000; 275(26): 19819 - 19823.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Renal Physiol.Home page
D. A. Bushinsky, W. R. Parker, K. M. Alexander, and N. S. Krieger
Metabolic, but not respiratory, acidosis increases bone PGE2 levels and calcium release
Am J Physiol Renal Physiol, December 1, 2001; 281(6): F1058 - F1066.
[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 © 1997 by The Endocrine Society