Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

Genetos, Damian C.; Yellowley, Clare E.; Loots, Gabriela G.

doi:10.1371/journal.pone.0017772

Prostaglandin E2 Signals Through PTGER2 to Regulate Sclerostin Expression

Journal Article · Wed Mar 16 00:00:00 EDT 2011 · PLoS ONE

DOI:https://doi.org/10.1371/journal.pone.0017772· OSTI ID:1627449

Genetos, Damian C. ^[1]; Yellowley, Clare E. ^[2]; Loots, Gabriela G. ^[3]

Univ. of California, Davis, CA (United States). School of Veterinary Medicine. Dept. of Anatomy, Physiology, and Cell Biology; DOE/OSTI
Univ. of California, Davis, CA (United States). School of Veterinary Medicine. Dept. of Anatomy, Physiology, and Cell Biology
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Biology and Biotechnology Division

The Wnt signaling pathway is a robust regulator of skeletal homeostasis. Gain-of-function mutations promote high bone mass, whereas loss of Lrp5 or Lrp6 co-receptors decrease bone mass. Similarly, mutations in antagonists of Wnt signaling influence skeletal integrity, in an inverse relation to Lrp receptor mutations. Loss of the Wnt antagonist Sclerostin (Sost) produces the generalized skeletal hyperostotic condition of sclerosteosis, which is characterized by increased bone mass and density due to hyperactive osteoblast function. Here we demonstrate that prostaglandin E2 (PGE2), a paracrine factor with pleiotropic effects on osteoblasts and osteoclasts, decreases Sclerostin expression in osteoblastic UMR106.01 cells. Decreased Sost expression correlates with increased expression of Wnt/TCF target genes Axin2 and Tcf3. We also show that the suppressive effect of PGE2 is mediated through a cyclic AMP/PKA pathway. Furthermore, selective agonists for the PGE2 receptor EP2 mimic the effect of PGE2 upon Sost, and siRNA reduction in Ptger2 prevents PGE2-induced Sost repression. These results indicate a functional relationship between prostaglandins and the Wnt/b-catenin signaling pathway in bone.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division

Grant/Contract Number:: AC52-07NA27344

OSTI ID:: 1627449

Journal Information:: PLoS ONE, Journal Name: PLoS ONE Journal Issue: 3 Vol. 6; ISSN 1932-6203

Publisher:: Public Library of ScienceCopyright Statement

Country of Publication:: United States

Language:: English

References (79)

Discovery of a Potent and Selective Agonist of the Prostaglandin EP4 Receptor. Billot, Xavier; Chateauneuf, Anne; Chauret, Nathalie ChemInform, Vol. 34, Issue 29 https://doi.org/10.1002/chin.200329178	journal	July 2003
Inhibition of sclerostin by monoclonal antibody increases bone formation, bone mass, and bone strength in aged male rats Li, Xiaodong; Warmington, Kelly S.; Niu, Qing-Tian Journal of Bone and Mineral Research, Vol. 25, Issue 12 https://doi.org/10.1002/jbmr.182	journal	July 2010
Inducible cyclo-oxygenase (COX-2) mediates the induction of bone formation by mechanical loading in vivo Forwood, M. R. Journal of Bone and Mineral Research, Vol. 11, Issue 11 https://doi.org/10.1002/jbmr.5650111112	journal	November 1996
Hypoxia decreases sclerostin expression and increases Wnt signaling in osteoblasts Genetos, Damian C.; Toupadakis, Chrisoula A.; Raheja, Leah F. Journal of Cellular Biochemistry https://doi.org/10.1002/jcb.22559	journal	January 2010
Prostaglandin E2 stimulates DNA synthesis by a cyclic AMP-independent pathway in osteoblastic clone MC3T3-E1 cells Hakeda, Yoshiyuki; Yoshino, Takahiko; Natakani, Yoshinori Journal of Cellular Physiology, Vol. 128, Issue 2 https://doi.org/10.1002/jcp.1041280204	journal	August 1986
Hypoxia regulates PGE2 release and EP1 receptor expression in osteoblastic cells Lee, Christina M.; Genetos, Damian C.; You, Zongbing Journal of Cellular Physiology, Vol. 212, Issue 1 https://doi.org/10.1002/jcp.21017	journal	March 2007
Indomethacin modulation of load-related stimulation of new bone formationin vivo Pead, M. J.; Lanyon, L. E. Calcified Tissue International, Vol. 45, Issue 1 https://doi.org/10.1007/bf02556658	journal	January 1989
Microarray analysis of thapsigargin — induced stress to the endoplasmic reticulum of mouse osteoblasts Hamamura, Kazunori; Liu, Yunlong; Yokota, Hiroki Journal of Bone and Mineral Metabolism, Vol. 26, Issue 3 https://doi.org/10.1007/s00774-007-0825-1	journal	May 2008
Stimulation of bone formation by prostaglandin E2 Chyun, Yong S.; Raisz, Lawrence G. Prostaglandins, Vol. 27, Issue 1 https://doi.org/10.1016/0090-6980(84)90223-5	journal	January 1984
Effects of exogenous prostanoids on the proliferation of osteoblast-like cells in vitro Feyen, Jean H. M.; Di Bon, Alfredo; van der Plas, Arie Prostaglandins, Vol. 30, Issue 5 https://doi.org/10.1016/0090-6980(85)90011-5	journal	November 1985
Discovery of CP-533536: An EP2 receptor selective prostaglandin E2 (PGE2) agonist that induces local bone formation Cameron, Kimberly O.; Lefker, Bruce A.; Ke, Hua Z. Bioorganic & Medicinal Chemistry Letters, Vol. 19, Issue 7 https://doi.org/10.1016/j.bmcl.2009.01.059	journal	April 2009
SOST is a target gene for PTH in bone Keller, Hansjoerg; Kneissel, Michaela Bone, Vol. 37, Issue 2 https://doi.org/10.1016/j.bone.2005.03.018	journal	August 2005
Prostaglandins in bone: bad cop, good cop? Blackwell, Katherine A.; Raisz, Lawrence G.; Pilbeam, Carol C. Trends in Endocrinology & Metabolism, Vol. 21, Issue 5 https://doi.org/10.1016/j.tem.2009.12.004	journal	May 2010
Genetic evidence that SOST inhibits WNT signaling in the limb Collette, Nicole M.; Genetos, Damian C.; Murugesh, Deepa Developmental Biology, Vol. 342, Issue 2 https://doi.org/10.1016/j.ydbio.2010.03.021	journal	June 2010
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development Gong, Yaoqin; Slee, Roger B.; Fukai, Naomi Cell, Vol. 107, Issue 4 https://doi.org/10.1016/s0092-8674(01)00571-2	journal	November 2001
An EP2 receptor-selective prostaglandin E2 agonist induces bone healing Paralkar, V. M.; Borovecki, F.; Ke, H. Z. Proceedings of the National Academy of Sciences, Vol. 100, Issue 11 https://doi.org/10.1073/pnas.1037343100	journal	May 2003
Ca2+-dependent Gene Expression Mediated by MEF2 Transcription Factors Blaeser, Frank; Ho, Nga; Prywes, Ron Journal of Biological Chemistry, Vol. 275, Issue 1 https://doi.org/10.1074/jbc.275.1.197	journal	January 2000
Sclerostin Is a Novel Secreted Osteoclast-derived Bone Morphogenetic Protein Antagonist with Unique Ligand Specificity Kusu, Naoki; Laurikkala, Johanna; Imanishi, Mayumi Journal of Biological Chemistry, Vol. 278, Issue 26 https://doi.org/10.1074/jbc.m301716200	journal	April 2003
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling Li, Xiaofeng; Zhang, Yazhou; Kang, Heeseog Journal of Biological Chemistry, Vol. 280, Issue 20 https://doi.org/10.1074/jbc.m413274200	journal	March 2005
Essential Role of β-Catenin in Postnatal Bone Acquisition Holmen, Sheri L.; Zylstra, Cassandra R.; Mukherjee, Aditi Journal of Biological Chemistry, Vol. 280, Issue 22 https://doi.org/10.1074/jbc.m501900200	journal	June 2005
SOST Is a Ligand for LRP5/LRP6 and a Wnt Signaling Inhibitor Semënov, Mikhail; Tamai, Keiko; He, Xi Journal of Biological Chemistry, Vol. 280, Issue 29 https://doi.org/10.1074/jbc.m504308200	journal	May 2005
The Wnt Co-receptor LRP5 Is Essential for Skeletal Mechanotransduction but Not for the Anabolic Bone Response to Parathyroid Hormone Treatment Sawakami, Kimihiko; Robling, Alexander G.; Ai, Minrong Journal of Biological Chemistry, Vol. 281, Issue 33 https://doi.org/10.1074/jbc.m601000200	journal	June 2006
LRP5 Mutations Linked to High Bone Mass Diseases Cause Reduced LRP5 Binding and Inhibition by SOST Semenov, Mikhail V.; He, Xi Journal of Biological Chemistry, Vol. 281, Issue 50 https://doi.org/10.1074/jbc.m609509200	journal	October 2006
Prostaglandin E Receptors Sugimoto, Yukihiko; Narumiya, Shuh Journal of Biological Chemistry, Vol. 282, Issue 16 https://doi.org/10.1074/jbc.r600038200	journal	February 2007
Cbfa1 -independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor Kato, Masaki; Patel, Millan S.; Levasseur, Regis The Journal of Cell Biology, Vol. 157, Issue 2 https://doi.org/10.1083/jcb.200201089	journal	April 2002
Localization of the Gene for Sclerosteosis to the van Buchem Disease–Gene Region on Chromosome 17q12–q21 Balemans, Wendy; Van Den Ende, Jenneke; Freire Paes-Alves, Auristela The American Journal of Human Genetics, Vol. 64, Issue 6 https://doi.org/10.1086/302416	journal	June 1999
A Mutation in the LDL Receptor–Related Protein 5 Gene Results in the Autosomal Dominant High–Bone-Mass Trait Little, Randall D.; Folz, Colleen; Manning, Susan P. The American Journal of Human Genetics, Vol. 70, Issue 1 https://doi.org/10.1086/338450	journal	January 2002
MEF2 responds to multiple calcium-regulated signals in the control of skeletal muscle fiber type Wu, H. The EMBO Journal, Vol. 19, Issue 9 https://doi.org/10.1093/emboj/19.9.1963	journal	May 2000
Osteocyte control of bone formation via sclerostin, a novel BMP antagonist Winkler, D. G. The EMBO Journal, Vol. 22, Issue 23 https://doi.org/10.1093/emboj/cdg599	journal	December 2003
Increased bone density in sclerosteosis is due to the deficiency of a novel secreted protein (SOST) Balemans, W. Human Molecular Genetics, Vol. 10, Issue 5 https://doi.org/10.1093/hmg/10.5.537	journal	March 2001
Sclerostin is a delayed secreted product of osteocytes that inhibits bone formation Poole, Kenneth E. S.; van Bezooijen, Rutger L.; Loveridge, Nigel The FASEB Journal, Vol. 19, Issue 13 https://doi.org/10.1096/fj.05-4221fje	journal	November 2005
Genomic deletion of a long-range bone enhancer misregulates sclerostin in Van Buchem disease Loots, G. G. Genome Research, Vol. 15, Issue 7 https://doi.org/10.1101/gr.3437105	journal	June 2005
Characterization of prostanoid relaxant/inhibitory receptors (ψ) using a highly selective agonist, TR4979 Gardiner, P. J. British Journal of Pharmacology, Vol. 87, Issue 1 https://doi.org/10.1111/j.1476-5381.1986.tb10155.x	journal	January 1986
Ca ²⁺ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts Chen, Neal X.; Ryder, Kimberly D.; Pavalko, Fredrick M. American Journal of Physiology-Cell Physiology, Vol. 278, Issue 5 https://doi.org/10.1152/ajpcell.2000.278.5.c989	journal	May 2000
Chronic Elevation of Parathyroid Hormone in Mice Reduces Expression of Sclerostin by Osteocytes: A Novel Mechanism for Hormonal Control of Osteoblastogenesis Bellido, T.; Ali, A. A.; Gubrij, I. Endocrinology, Vol. 146, Issue 11 https://doi.org/10.1210/en.2005-0239	journal	November 2005
Stimulation of bone nodule formation in vitro by prostaglandins E1 and E2. Flanagan, A. M.; Chambers, T. J. Endocrinology, Vol. 130, Issue 1 https://doi.org/10.1210/endo.130.1.1309342	journal	January 1992
Regulation of the two prostaglandin G/H synthases by parathyroid hormone, interleukin-1, cortisol, and prostaglandin E2 in cultured neonatal mouse calvariae. Kawaguchi, H.; Raisz, L. G.; Voznesensky, O. S. Endocrinology, Vol. 135, Issue 3 https://doi.org/10.1210/endo.135.3.8070358	journal	September 1994
The Wnt Antagonist Secreted Frizzled-Related Protein-1 Is a Negative Regulator of Trabecular Bone Formation in Adult Mice Bodine, Peter V. N.; Zhao, Weiguang; Kharode, Yogendra P. Molecular Endocrinology, Vol. 18, Issue 5 https://doi.org/10.1210/me.2003-0498	journal	May 2004
BMP signaling negatively regulates bone mass through sclerostin by inhibiting the canonical Wnt pathway Kamiya, N.; Ye, L.; Kobayashi, T. Development, Vol. 135, Issue 22 https://doi.org/10.1242/dev.025825	journal	November 2008
Decreased BMD and Limb Deformities in Mice Carrying Mutations in Both Lrp5 and Lrp6 Holmen, Sheri L.; Giambernardi, Troy A.; Zylstra, Cassandra R. Journal of Bone and Mineral Research, Vol. 19, Issue 12 https://doi.org/10.1359/jbmr.040907	journal	September 2004
Bone Density Ligand, Sclerostin, Directly Interacts With LRP5 but Not LRP5G171V to Modulate Wnt Activity Ellies, Debra L.; Viviano, Beth; McCarthy, John Journal of Bone and Mineral Research, Vol. 21, Issue 11 https://doi.org/10.1359/jbmr.060810	journal	August 2006
Targeted Deletion of the Sclerostin Gene in Mice Results in Increased Bone Formation and Bone Strength Li, Xiaodong; Ominsky, Michael S.; Niu, Qing-Tian Journal of Bone and Mineral Research, Vol. 23, Issue 6 https://doi.org/10.1359/jbmr.080216	journal	February 2008
Inhibiting the Inhibitor: A New Route to Bone Anabolism Jilka, Robert L. Journal of Bone and Mineral Research, Vol. 24, Issue 4 https://doi.org/10.1359/jbmr.090228	journal	April 2009
Pulsating Fluid Flow Stimulates Prostaglandin Release and Inducible Prostaglandin G/H Synthase mRNA Expression in Primary Mouse Bone Cells Klein-Nulend, Jenneke; Burger, Elisabeth H.; Semeins, Cornelis M. Journal of Bone and Mineral Research, Vol. 12, Issue 1 https://doi.org/10.1359/jbmr.1997.12.1.45	journal	January 1997
Fluid Flow Induction of Cyclo-Oxygenase 2 Gene Expression in Osteoblasts Is Dependent on an Extracellular Signal-Regulated Kinase Signaling Pathway Wadhwa, Sunil; Godwin, Stephen L.; Peterson, Donald R. Journal of Bone and Mineral Research, Vol. 17, Issue 2 https://doi.org/10.1359/jbmr.2002.17.2.266	journal	February 2002
A Novel, Non-Prostanoid EP2 Receptor-Selective Prostaglandin E2 Agonist Stimulates Local Bone Formation and Enhances Fracture Healing Li, Mei; Ke, Hua Zhu; Qi, Hong Journal of Bone and Mineral Research, Vol. 18, Issue 11 https://doi.org/10.1359/jbmr.2003.18.11.2033	journal	November 2003
Control of Bone Mass and Remodeling by PTH Receptor Signaling in Osteocytes O'Brien, Charles A.; Plotkin, Lilian I.; Galli, Carlo PLoS ONE, Vol. 3, Issue 8 https://doi.org/10.1371/journal.pone.0002942	journal	August 2008
The Wnt antagonist secreted frizzled-related protein-1 controls osteoblast and osteocyte apoptosis Bodine, Peter V. N.; Billiard, Julia; Moran, Robert A. Journal of Cellular Biochemistry, Vol. 96, Issue 6 https://doi.org/10.1002/jcb.20599	journal	December 2005
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method Livak, Kenneth J.; Schmittgen, Thomas D. Methods, Vol. 25, Issue 4 https://doi.org/10.1006/meth.2001.1262	journal	December 2001
Indomethacin modulation of load-related stimulation of new bone formationin vivo Pead, M. J.; Lanyon, L. E. Calcified Tissue International, Vol. 45, Issue 1 https://doi.org/10.1007/BF02556658	journal	January 1989
Wnt signaling and osteoblastogenesis Bodine, Peter V. N.; Komm, Barry S. Reviews in Endocrine and Metabolic Disorders, Vol. 7, Issue 1-2 https://doi.org/10.1007/s11154-006-9002-4	journal	September 2006
LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development Gong, Yaoqin; Slee, Roger B.; Fukai, Naomi Cell, Vol. 107, Issue 4 https://doi.org/10.1016/S0092-8674(01)00571-2	journal	November 2001
WNT targets: repression and activation Nusse, Roel Trends in Genetics, Vol. 15, Issue 1 https://doi.org/10.1016/S0168-9525(98)01634-5	journal	January 1999
Discovery of a potent and selective agonist of the prostaglandin EP4 receptor Billot, Xavier; Chateauneuf, Anne; Chauret, Nathalie Bioorganic & Medicinal Chemistry Letters, Vol. 13, Issue 6 https://doi.org/10.1016/S0960-894X(03)00042-8	journal	March 2003
Wnt/β-catenin signaling Akiyama, Tetsu Cytokine & Growth Factor Reviews, Vol. 11, Issue 4 https://doi.org/10.1016/S1359-6101(00)00011-3	journal	December 2000
The in vivo anabolic actions of prostaglandins in bone Jee, W. S. S.; Ma, Y. F. Bone, Vol. 21, Issue 4 https://doi.org/10.1016/S8756-3282(97)00147-6	journal	October 1997
EP2 and EP4 receptors differentially mediate MAPK pathways underlying anabolic actions of prostaglandin E2 on bone formation in rat calvaria cell cultures Minamizaki, Tomoko; Yoshiko, Yuji; Kozai, Katsuyuki Bone, Vol. 44, Issue 6 https://doi.org/10.1016/j.bone.2009.02.010	journal	June 2009
New technologies for the enhancement of skeletal repair William Axelrad, T.; Kakar, Sanjeev; Einhorn, Thomas A. Injury, Vol. 38, Issue 1 https://doi.org/10.1016/j.injury.2007.02.010	journal	March 2007
Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells Kiriyama, Michitaka; Ushikubi, Fumitaka; Kobayashi, Takuya British Journal of Pharmacology, Vol. 122, Issue 2 https://doi.org/10.1038/sj.bjp.0701367	journal	September 1997
Sclerostin Is a Novel Secreted Osteoclast-derived Bone Morphogenetic Protein Antagonist with Unique Ligand Specificity Kusu, Naoki; Laurikkala, Johanna; Imanishi, Mayumi Journal of Biological Chemistry, Vol. 278, Issue 26 https://doi.org/10.1074/jbc.M301716200	journal	April 2003
Sclerostin Binds to LRP5/6 and Antagonizes Canonical Wnt Signaling Li, Xiaofeng; Zhang, Yazhou; Kang, Heeseog Journal of Biological Chemistry, Vol. 280, Issue 20 https://doi.org/10.1074/jbc.M413274200	journal	March 2005
Essential Role of β-Catenin in Postnatal Bone Acquisition Holmen, Sheri L.; Zylstra, Cassandra R.; Mukherjee, Aditi Journal of Biological Chemistry, Vol. 280, Issue 22 https://doi.org/10.1074/jbc.M501900200	journal	June 2005
SOST Is a Ligand for LRP5/LRP6 and a Wnt Signaling Inhibitor Semënov, Mikhail; Tamai, Keiko; He, Xi Journal of Biological Chemistry, Vol. 280, Issue 29 https://doi.org/10.1074/jbc.M504308200	journal	May 2005
The Wnt Co-receptor LRP5 Is Essential for Skeletal Mechanotransduction but Not for the Anabolic Bone Response to Parathyroid Hormone Treatment Sawakami, Kimihiko; Robling, Alexander G.; Ai, Minrong Journal of Biological Chemistry, Vol. 281, Issue 33 https://doi.org/10.1074/jbc.M601000200	journal	June 2006
LRP5 Mutations Linked to High Bone Mass Diseases Cause Reduced LRP5 Binding and Inhibition by SOST Semenov, Mikhail V.; He, Xi Journal of Biological Chemistry, Vol. 281, Issue 50 https://doi.org/10.1074/jbc.M609509200	journal	October 2006
Prostaglandin E Receptors Sugimoto, Yukihiko; Narumiya, Shuh Journal of Biological Chemistry, Vol. 282, Issue 16 https://doi.org/10.1074/jbc.R600038200	journal	February 2007
Bone Dysplasia Sclerosteosis Results from Loss of the SOST Gene Product, a Novel Cystine Knot–Containing Protein Brunkow, Mary E.; Gardner, Jessica C.; Van Ness, Jeff The American Journal of Human Genetics, Vol. 68, Issue 3 https://doi.org/10.1086/318811	journal	March 2001
Inductive Effects of Prostaglandins on Alkaline Phosphatase in Osteoblastic Cells, Clone MC3T3-E11 Hakeda, Yoshiyuki; Nakatani, Yoshinori; Hiramatsu, Masahiko The Journal of Biochemistry, Vol. 97, Issue 1 https://doi.org/10.1093/oxfordjournals.jbchem.a135072	journal	January 1985
Ca ²⁺ regulates fluid shear-induced cytoskeletal reorganization and gene expression in osteoblasts Chen, Neal X.; Ryder, Kimberly D.; Pavalko, Fredrick M. American Journal of Physiology-Cell Physiology, Vol. 278, Issue 5 https://doi.org/10.1152/ajpcell.2000.278.5.C989	journal	May 2000
Prostaglandin E receptor subtypes in mouse osteoblastic cell line. Suda, M.; Tanaka, K.; Natsui, K. Endocrinology, Vol. 137, Issue 5 https://doi.org/10.1210/endo.137.5.8612504	journal	May 1996
Nonunion of the femoral diaphysis: THE INFLUENCE OF REAMING AND NON-STEROIDAL ANTI-INFLAMMATORY DRUGS Giannoudis, P. V.; MacDonald, D. A.; Matthews, S. J. The Journal of Bone and Joint Surgery. British volume, Vol. 82-B, Issue 5 https://doi.org/10.1302/0301-620X.82B5.0820655	journal	July 2000
Heterotopic ossification prophylaxis with indomethacin increases the risk of long-bone nonunion Burd, T. A.; Hughes, M. S.; Anglen, J. O. The Journal of Bone and Joint Surgery. British volume, Vol. 85-B, Issue 5 https://doi.org/10.1302/0301-620X.85B5.13970	journal	July 2003
Deletion of a Single Allele of the Dkk1 Gene Leads to an Increase in Bone Formation and Bone Mass Morvan, Frederic; Boulukos, Kim; Clément-Lacroix, Philippe Journal of Bone and Mineral Research, Vol. 21, Issue 6 https://doi.org/10.1359/jbmr.060311	journal	May 2006
Control of the SOST Bone Enhancer by PTH Using MEF2 Transcription Factors Leupin, Olivier; Kramer, Ina; Collette, Nicole M. Journal of Bone and Mineral Research, Vol. 22, Issue 12 https://doi.org/10.1359/jbmr.070804	journal	August 2007
Sclerostin Antibody Treatment Increases Bone Formation, Bone Mass, and Bone Strength in a Rat Model of Postmenopausal Osteoporosis* Li, Xiaodong; Ominsky, Michael S.; Warmington, Kelly S. Journal of Bone and Mineral Research, Vol. 24, Issue 4 https://doi.org/10.1359/jbmr.081206	journal	April 2009
Cyclo-Oxygenase 2 Function Is Essential for Bone Fracture Healing Simon, Ann Marie; Manigrasso, Michaele Beth; O'Connor, J. Patrick Journal of Bone and Mineral Research, Vol. 17, Issue 6 https://doi.org/10.1359/jbmr.2002.17.6.963	journal	June 2002
COX inhibitors and their effects on bone healing Gerstenfeld, Louis C.; Einhorn, Thomas A. Expert Opinion on Drug Safety, Vol. 3, Issue 2 https://doi.org/10.1517/14740338.3.2.131	journal	March 2004
Bone formation induced in an infant by systemic prostaglandin-E ₂ administration Jørgensen, Hans R. I.; Svanholm, Hans; Høst, Arne Acta Orthopaedica Scandinavica, Vol. 59, Issue 4 https://doi.org/10.3109/17453678809149406	journal	January 1988
Modulation of sclerostin expression by mechanical loading and bone morphogenetic proteins in osteogenic cells Papanicolaou, Savvas E.; Phipps, Roger J.; Fyhrie, David P. Biorheology, Vol. 46, Issue 5 https://doi.org/10.3233/BIR-2009-0550	journal	January 2009

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