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Title: Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone

Abstract

During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineralmore » concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility.« less

Authors:
 [1];  [2];  [3];  [4];  [1];  [1];  [1];  [1];  [2];  [4];  [5];  [5];  [6];  [3];  [5];  [2];  [1];  [2]
+ Show Author Affiliations
  1. University of Virginia, Charlottesville, VA (United States)
  2. University of California, San Francisco, CA (United States)
  3. University of California, Berkeley, CA (United States)
  4. Scios, Inc, Fremont, CA (United States)
  5. University of Arkansas, Little Rock, AR (United States)
  6. Scios, Inc, Fremont, CA (United States); Pfizer RTC, Cambridge, MA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health(NIH); Arthritis Foundation; Sandler Family Foundation; Carl Nelson Chair; Stugis Foundation; Aurbach Endowment
OSTI Identifier:
1627370
Grant/Contract Number:  
AC02-05CH11231
Resource Type:
Accepted Manuscript
Journal Name:
PLoS ONE
Additional Journal Information:
Journal Volume: 4; Journal Issue: 4; Journal ID: ISSN 1932-6203
Publisher:
Public Library of Science
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; osteoclasts; osteoblasts; bone fracture; osteoblast differentiation; femur; signal inhibition

Citation Formats

Mohammad, Khalid S., Chen, Carol G., Balooch, Guive, Stebbins, Elizabeth, McKenna, C. Ryan, Davis, Holly, Niewolna, Maria, Peng, Xiang Hong, Nguyen, Daniel H. N., Ionova-Martin, Sophi S., Bracey, John W., Hogue, William R., Wong, Darren H., Ritchie, Robert O., Suva, Larry J., Derynck, Rik, Guise, Theresa A., and Alliston, Tamara. Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone. United States: N. p., 2009. Web. doi:10.1371/journal.pone.0005275.
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Mohammad, Khalid S., Chen, Carol G., Balooch, Guive, Stebbins, Elizabeth, McKenna, C. Ryan, Davis, Holly, Niewolna, Maria, Peng, Xiang Hong, Nguyen, Daniel H. N., Ionova-Martin, Sophi S., Bracey, John W., Hogue, William R., Wong, Darren H., Ritchie, Robert O., Suva, Larry J., Derynck, Rik, Guise, Theresa A., & Alliston, Tamara. Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone. United States. https://doi.org/10.1371/journal.pone.0005275
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Mohammad, Khalid S., Chen, Carol G., Balooch, Guive, Stebbins, Elizabeth, McKenna, C. Ryan, Davis, Holly, Niewolna, Maria, Peng, Xiang Hong, Nguyen, Daniel H. N., Ionova-Martin, Sophi S., Bracey, John W., Hogue, William R., Wong, Darren H., Ritchie, Robert O., Suva, Larry J., Derynck, Rik, Guise, Theresa A., and Alliston, Tamara. Thu . "Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone". United States. https://doi.org/10.1371/journal.pone.0005275. https://www.osti.gov/servlets/purl/1627370.
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@article{osti_1627370,
title = {Pharmacologic Inhibition of the TGF-β Type I Receptor Kinase Has Anabolic and Anti-Catabolic Effects on Bone},
author = {Mohammad, Khalid S. and Chen, Carol G. and Balooch, Guive and Stebbins, Elizabeth and McKenna, C. Ryan and Davis, Holly and Niewolna, Maria and Peng, Xiang Hong and Nguyen, Daniel H. N. and Ionova-Martin, Sophi S. and Bracey, John W. and Hogue, William R. and Wong, Darren H. and Ritchie, Robert O. and Suva, Larry J. and Derynck, Rik and Guise, Theresa A. and Alliston, Tamara},
abstractNote = {During development, growth factors and hormones cooperate to establish the unique sizes, shapes and material properties of individual bones. Among these, TGF-β has been shown to developmentally regulate bone mass and bone matrix properties. However, the mechanisms that control postnatal skeletal integrity in a dynamic biological and mechanical environment are distinct from those that regulate bone development. In addition, despite advances in understanding the roles of TGF-β signaling in osteoblasts and osteoclasts, the net effects of altered postnatal TGF-β signaling on bone remain unclear. To examine the role of TGF-β in the maintenance of the postnatal skeleton, we evaluated the effects of pharmacological inhibition of the TGF-β type I receptor (TβRI) kinase on bone mass, architecture and material properties. Inhibition of TβRI function increased bone mass and multiple aspects of bone quality, including trabecular bone architecture and macro-mechanical behavior of vertebral bone. TβRI inhibitors achieved these effects by increasing osteoblast differentiation and bone formation, while reducing osteoclast differentiation and bone resorption. Furthermore, they induced the expression of Runx2 and EphB4, which promote osteoblast differentiation, and ephrinB2, which antagonizes osteoclast differentiation. Through these anabolic and anti-catabolic effects, TβRI inhibitors coordinate changes in multiple bone parameters, including bone mass, architecture, matrix mineral concentration and material properties, that collectively increase bone fracture resistance. Therefore, TβRI inhibitors may be effective in treating conditions of skeletal fragility.},
doi = {10.1371/journal.pone.0005275},
journal = {PLoS ONE},
number = 4,
volume = 4,
place = {United States},
year = {Thu Apr 16 00:00:00 EDT 2009},
month = {Thu Apr 16 00:00:00 EDT 2009}
}
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Works referenced in this record:

Inhibition of TGF-beta receptor signaling in osteoblasts leads to decreased bone remodeling and increased trabecular bone mass
journal, October 1999

A biomechanical perspective on bone quality
journal, December 2006

Inhibition of Transforming Growth Factor β Signaling Reduces Pancreatic Adenocarcinoma Growth and Invasiveness
journal, March 2007

  • Gaspar, Nicholas J.; Li, Lingyun; Kapoun, Ann M.
  • Molecular Pharmacology, Vol. 72, Issue 1
  • DOI: 10.1124/mol.106.029025

Roles of stromal cell RANKL, OPG, and M‐CSF expression in biphasic TGF‐β regulation of osteoclast differentiation
journal, February 2004

  • Karst, Mary; Gorny, Genevieve; Galvin, Rachelle J. Sells
  • Journal of Cellular Physiology, Vol. 200, Issue 1
  • DOI: 10.1002/jcp.20036

The design of mineralised hard tissues for their mechanical functions
journal, December 1999

Elastic properties of human cortical and trabecular lamellar bone measured by nanoindentation
journal, October 1997

Regulation of bone mass by Wnt signaling
journal, May 2006

  • Krishnan, V.
  • Journal of Clinical Investigation, Vol. 116, Issue 5
  • DOI: 10.1172/JCI28551

Osteoclast synthesis and secretion and activation of latent transforming growth factor β
journal, April 1994

Inhibin Suppresses and Activin Stimulates Osteoblastogenesis and Osteoclastogenesis in Murine Bone Marrow Cultures
journal, January 2002

Osteoblastic Responses to TGF-β during Bone Remodeling
journal, July 1998

  • Erlebacher, Adrian; Filvaroff, Ellen H.; Ye, Jian-Qin
  • Molecular Biology of the Cell, Vol. 9, Issue 7
  • DOI: 10.1091/mbc.9.7.1903

Proteolysis of Latent Transforming Growth Factor-β (TGF-β)-binding Protein-1 by Osteoclasts
journal, June 2002

  • Dallas, Sarah L.; Rosser, Jennifer L.; Mundy, Gregory R.
  • Journal of Biological Chemistry, Vol. 277, Issue 24
  • DOI: 10.1074/jbc.M111663200

BMP signaling in skeletal development
journal, March 2005

Current insights into the role of transforming growth factor-β in bone resorption
journal, November 2005

  • Fox, Simon W.; Lovibond, Alison C.
  • Molecular and Cellular Endocrinology, Vol. 243, Issue 1-2
  • DOI: 10.1016/j.mce.2005.09.008

Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin
journal, June 1994

Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure
journal, June 2006

  • Arany, P. R.; Flanders, K. C.; Kobayashi, T.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 24
  • DOI: 10.1073/pnas.0602473103

Transforming Growth Factor-β1 Increases mRNA Levels of Osteoclastogenesis Inhibitory Factor in Osteoblastic/Stromal Cells and Inhibits the Survival of Murine Osteoclast-like Cells
journal, November 1998

  • Murakami, Takehiko; Yamamoto, Michiko; Yamamoto, Mikio
  • Biochemical and Biophysical Research Communications, Vol. 252, Issue 3
  • DOI: 10.1006/bbrc.1998.9723

Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.
journal, January 1996

The relationship between the stiffness and the mineral content of bone
journal, October 1969

Inhibin A Is an Endocrine Stimulator of Bone Mass and Strength
journal, April 2007

  • Perrien, Daniel S.; Akel, Nisreen S.; Edwards, Paul K.
  • Endocrinology, Vol. 148, Issue 4
  • DOI: 10.1210/en.2006-0848

Transforming Growth Factor-β1 to the Bone
journal, October 2005

  • Janssens, Katrien; ten Dijke, Peter; Janssens, Sophie
  • Endocrine Reviews, Vol. 26, Issue 6
  • DOI: 10.1210/er.2004-0001

Endogenous TGF-β signaling suppresses maturation of osteoblastic mesenchymal cells
journal, January 2004

TGF-  regulates the mechanical properties and composition of bone matrix
journal, December 2005

  • Balooch, G.; Balooch, M.; Nalla, R. K.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 52
  • DOI: 10.1073/pnas.0507417102

Bidirectional ephrinB2-EphB4 signaling controls bone homeostasis
journal, August 2006

Measurement of hardness and elastic modulus by instrumented indentation: Advances in understanding and refinements to methodology
journal, January 2004

Platelet Dysfunction and a High Bone Mass Phenotype in a Murine Model of Platelet-Type von Willebrand Disease
journal, February 2008

  • Suva, Larry J.; Hartman, Eric; Dilley, Joshua D.
  • The American Journal of Pathology, Vol. 172, Issue 2
  • DOI: 10.2353/ajpath.2008.070417

Direct Three-Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus
journal, July 1999

  • Hildebrand, Tor; Laib, Andres; Müller, Ralph
  • Journal of Bone and Mineral Research, Vol. 14, Issue 7
  • DOI: 10.1359/jbmr.1999.14.7.1167

Global Analysis of Smad2/3-Dependent TGF-β Signaling in Living Mice Reveals Prominent Tissue-Specific Responses to Injury
journal, June 2005

TGF-β/Smad3 Signals Repress Chondrocyte Hypertrophic Differentiation and Are Required for Maintaining Articular Cartilage
journal, March 2001

  • Yang, Xiao; Chen, Lin; Xu, Xiaoling
  • Journal of Cell Biology, Vol. 153, Issue 1
  • DOI: 10.1083/jcb.153.1.35

The Loss of Smad3 Results in a Lower Rate of Bone Formation and Osteopenia Through Dysregulation of Osteoblast Differentiation and Apoptosis
journal, October 2001

  • Borton, Anita J.; Frederick, Joshua P.; Datto, Michael B.
  • Journal of Bone and Mineral Research, Vol. 16, Issue 10
  • DOI: 10.1359/jbmr.2001.16.10.1754

Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee
journal, December 1987

  • Parfitt, A. Michael; Drezner, Marc K.; Glorieux, Francis H.
  • Journal of Bone and Mineral Research, Vol. 2, Issue 6
  • DOI: 10.1002/jbmr.5650020617

Repression of Runx2 function by TGF-β through recruitment of class II histone deacetylases by Smad3
journal, June 2005

Bone histomorphometry: Standardization of nomenclature, symbols, and units: Report of the asbmr histomorphometry nomenclature committee
journal, December 1987

  • Parfitt, A. Michael; Drezner, Marc K.; Glorieux, Francis H.
  • Journal of Bone and Mineral Research, Vol. 2, Issue 6
  • DOI: 10.1002/jbmr.5650020617

Osteoclast synthesis and secretion and activation of latent transforming growth factor β
journal, April 1994

Transforming Growth Factor-β1 Increases mRNA Levels of Osteoclastogenesis Inhibitory Factor in Osteoblastic/Stromal Cells and Inhibits the Survival of Murine Osteoclast-like Cells
journal, November 1998

  • Murakami, Takehiko; Yamamoto, Michiko; Yamamoto, Mikio
  • Biochemical and Biophysical Research Communications, Vol. 252, Issue 3
  • DOI: 10.1006/bbrc.1998.9723

Activation of the bone-derived latent TGF beta complex by isolated osteoclasts
journal, February 1989

  • Oreffo, Richard O. C.; Mundy, Gregory R.; Seyedin, Saeid M.
  • Biochemical and Biophysical Research Communications, Vol. 158, Issue 3
  • DOI: 10.1016/0006-291x(89)92795-2

The relationship between the stiffness and the mineral content of bone
journal, October 1969

BMP signaling in skeletal development
journal, March 2005

A biomechanical perspective on bone quality
journal, December 2006

Boning up on Ephrin Signaling
journal, August 2006

Elastic modulus and hardness of cortical and trabecular bone lamellae measured by nanoindentation in the human femur
journal, October 1999

Decreased bone mass and bone elasticity in mice lacking the transforming growth factor-β1 gene
journal, August 1998

Development of TGF-β signalling inhibitors for cancer therapy
journal, December 2004

  • Yingling, Jonathan M.; Blanchard, Kerry L.; Sawyer, J. Scott
  • Nature Reviews Drug Discovery, Vol. 3, Issue 12
  • DOI: 10.1038/nrd1580

TGF-  regulates the mechanical properties and composition of bone matrix
journal, December 2005

  • Balooch, G.; Balooch, M.; Nalla, R. K.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 52
  • DOI: 10.1073/pnas.0507417102

Smad3 deficiency alters key structural elements of the extracellular matrix and mechanotransduction of wound closure
journal, June 2006

  • Arany, P. R.; Flanders, K. C.; Kobayashi, T.
  • Proceedings of the National Academy of Sciences, Vol. 103, Issue 24
  • DOI: 10.1073/pnas.0602473103

Transforming Growth Factor-β Controls Human Osteoclastogenesis through the p38 MAPK and Regulation of RANK Expression
journal, November 2003

  • Karsdal, Morten A.; Hjorth, Pernille; Henriksen, Kim
  • Journal of Biological Chemistry, Vol. 278, Issue 45
  • DOI: 10.1074/jbc.m303905200

Increased expression of TGF-beta 2 in osteoblasts results in an osteoporosis-like phenotype.
journal, January 1996

TGF-β/Smad3 Signals Repress Chondrocyte Hypertrophic Differentiation and Are Required for Maintaining Articular Cartilage
journal, March 2001

  • Yang, Xiao; Chen, Lin; Xu, Xiaoling
  • Journal of Cell Biology, Vol. 153, Issue 1
  • DOI: 10.1083/jcb.153.1.35

Osteoblastic Responses to TGF-β during Bone Remodeling
journal, July 1998

  • Erlebacher, Adrian; Filvaroff, Ellen H.; Ye, Jian-Qin
  • Molecular Biology of the Cell, Vol. 9, Issue 7
  • DOI: 10.1091/mbc.9.7.1903

Inhibition of Transforming Growth Factor β Signaling Reduces Pancreatic Adenocarcinoma Growth and Invasiveness
journal, March 2007

  • Gaspar, Nicholas J.; Li, Lingyun; Kapoun, Ann M.
  • Molecular Pharmacology, Vol. 72, Issue 1
  • DOI: 10.1124/mol.106.029025

Type I receptors specify growth-inhibitory and transcriptional responses to transforming growth factor beta and activin.
journal, June 1994

  • Cárcamo, J.; Weis, F. M.; Ventura, F.
  • Molecular and Cellular Biology, Vol. 14, Issue 6
  • DOI: 10.1128/mcb.14.6.3810

Progressive Transforming Growth Factor β1–induced Lung Fibrosis Is Blocked by an Orally Active ALK5 Kinase Inhibitor
journal, April 2005

  • Bonniaud, Philippe; Margetts, Peter J.; Kolb, Martin
  • American Journal of Respiratory and Critical Care Medicine, Vol. 171, Issue 8
  • DOI: 10.1164/rccm.200405-612oc

Transforming Growth Factor-β1 to the Bone
journal, October 2005

  • Janssens, Katrien; ten Dijke, Peter; Janssens, Sophie
  • Endocrine Reviews, Vol. 26, Issue 6
  • DOI: 10.1210/er.2004-0001

The design of mineralised hard tissues for their mechanical functions
journal, December 1999

Effects of Cyclic Versus Daily hPTH(1-34) Regimens on Bone Strength in Association With BMD, Biochemical Markers, and Bone Structure in Mice
journal, October 2005

  • Iida-Klein, Akiko; Hughes, Christine; Lu, Shi Shou
  • Journal of Bone and Mineral Research, Vol. 21, Issue 2
  • DOI: 10.1359/jbmr.051017

Direct Three-Dimensional Morphometric Analysis of Human Cancellous Bone: Microstructural Data from Spine, Femur, Iliac Crest, and Calcaneus
journal, July 1999

  • Hildebrand, Tor; Laib, Andres; Müller, Ralph
  • Journal of Bone and Mineral Research, Vol. 14, Issue 7
  • DOI: 10.1359/jbmr.1999.14.7.1167

The Loss of Smad3 Results in a Lower Rate of Bone Formation and Osteopenia Through Dysregulation of Osteoblast Differentiation and Apoptosis
journal, October 2001

  • Borton, Anita J.; Frederick, Joshua P.; Datto, Michael B.
  • Journal of Bone and Mineral Research, Vol. 16, Issue 10
  • DOI: 10.1359/jbmr.2001.16.10.1754
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    Works referencing / citing this record:

    Excess TGF-β mediates muscle weakness associated with bone metastases in mice
    journal, October 2015

    • Waning, David L.; Mohammad, Khalid S.; Reiken, Steven
    • Nature Medicine, Vol. 21, Issue 11
    • DOI: 10.1038/nm.3961

    Muscle and Bone Impairment in Children With Marfan Syndrome: Correlation With Age and FBN1 Genotype: MUSCLE AND BONE IMPAIRMENT IN MARFAN SYNDROME
    journal, May 2015

    • Haine, Elsa; Salles, Jean-Pierre; Khau Van Kien, Philippe
    • Journal of Bone and Mineral Research, Vol. 30, Issue 8
    • DOI: 10.1002/jbmr.2471

    Transcriptional downregulation of miR-133b by REST promotes prostate cancer metastasis to bone via activating TGF-β signaling
    journal, July 2018

    Cancer to bone: a fatal attraction
    journal, May 2011

    • Weilbaecher, Katherine N.; Guise, Theresa A.; McCauley, Laurie K.
    • Nature Reviews Cancer, Vol. 11, Issue 6
    • DOI: 10.1038/nrc3055

    Extracellular Microfibrils Control Osteoblast-supported Osteoclastogenesis by Restricting TGFβ Stimulation of RANKL Production
    journal, October 2010

    • Nistala, Harikiran; Lee-Arteaga, Sui; Smaldone, Silvia
    • Journal of Biological Chemistry, Vol. 285, Issue 44
    • DOI: 10.1074/jbc.m110.125328

    Role of bone-anabolic agents in the treatment of breast cancer bone metastases
    journal, December 2014

    Hypoxia and TGF-β Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment
    journal, September 2009

    Pharmacological and biological therapeutic strategies for osteogenesis imperfecta
    journal, November 2016

    • Marom, Ronit; Lee, Yi-Chien; Grafe, Ingo
    • American Journal of Medical Genetics Part C: Seminars in Medical Genetics, Vol. 172, Issue 4
    • DOI: 10.1002/ajmg.c.31532

    The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone
    journal, July 2017

    • Dai, Yuhu; Ren, Dong; Yang, Qing
    • British Journal of Cancer, Vol. 117, Issue 5
    • DOI: 10.1038/bjc.2017.212

    NanoLuc Reporter for Dual Luciferase Imaging in Living Animals
    journal, October 2013

    • Stacer, Amanda C.; Nyati, Shyam; Moudgil, Pranav
    • Molecular Imaging, Vol. 12, Issue 7
    • DOI: 10.2310/7290.2013.00062

    Cytogenetic and hematological alterations induced by acute oral exposure of imidacloprid in female mice
    journal, February 2015

    Role of TGF-β in a Mouse Model of High Turnover Renal Osteodystrophy: ROLE OF TGF-β IN RENAL OSTEODYSTROPHY
    journal, April 2014

    • Liu, Shiguang; Song, Wenping; Boulanger, Joseph H.
    • Journal of Bone and Mineral Research, Vol. 29, Issue 5
    • DOI: 10.1002/jbmr.2120

    Low bone mass and high material bone density in two patients with Loeys-Dietz syndrome caused by transforming growth factor beta receptor 2 mutations
    journal, February 2012

    • Ben Amor, I. Mouna; Edouard, Thomas; Glorieux, Francis H.
    • Journal of Bone and Mineral Research, Vol. 27, Issue 3
    • DOI: 10.1002/jbmr.1470

    Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity
    journal, June 2018

    • Asparuhova, Maria B.; Caballé-Serrano, Jordi; Buser, Daniel
    • International Journal of Oral Science, Vol. 10, Issue 2
    • DOI: 10.1038/s41368-018-0021-2

    Myeloma bone disease: pathogenesis, current treatments and future targets
    journal, September 2014

    • Walker, R. E.; Lawson, M. A.; Buckle, C. H.
    • British Medical Bulletin, Vol. 111, Issue 1
    • DOI: 10.1093/bmb/ldu016

    TGFβ Inhibition Stimulates Collagen Maturation to Enhance Bone Repair and Fracture Resistance in a Murine Myeloma Model
    journal, October 2019

    • Green, Alanna C.; Lath, Darren; Hudson, Katie
    • Journal of Bone and Mineral Research, Vol. 34, Issue 12
    • DOI: 10.1002/jbmr.3859

    Load Regulates Bone Formation and Sclerostin Expression through a TGFβ-Dependent Mechanism
    journal, January 2013

    Bone metastasis in prostate cancer: emerging therapeutic strategies
    journal, May 2011

    • Sturge, Justin; Caley, Matthew P.; Waxman, Jonathan
    • Nature Reviews Clinical Oncology, Vol. 8, Issue 6
    • DOI: 10.1038/nrclinonc.2011.67

    Inhibition of TGF-β signaling by 1D11 antibody treatment increases bone mass and quality in vivo: ANTI-TGF-β THERAPY INCREASES BONE
    journal, May 2010

    • Edwards, James R.; Nyman, Jeffry S.; Lwin, Seint T.
    • Journal of Bone and Mineral Research, Vol. 25, Issue 11
    • DOI: 10.1002/jbmr.139

    Differential stem- and progenitor-cell trafficking by prostaglandin E2
    journal, March 2013

    • Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha
    • Nature, Vol. 495, Issue 7441
    • DOI: 10.1038/nature11929

    The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part II (Differentiation)
    journal, February 2014

    • Dorst, Kathryn; Rammelkamp, Derek; Hadjiargyrou, Michael
    • Materials, Vol. 7, Issue 2
    • DOI: 10.3390/ma7021097

    Contribution of Bone Tissue Modulus to Breast Cancer Metastasis to Bone
    journal, July 2011

    The Contribution of the Extracellular Matrix to the Fracture Resistance of Bone
    journal, April 2012

    Bone metastasis: mechanisms and therapeutic opportunities
    journal, January 2011

    • Suva, Larry J.; Washam, Charity; Nicholas, Richard W.
    • Nature Reviews Endocrinology, Vol. 7, Issue 4
    • DOI: 10.1038/nrendo.2010.227

    Assessment of bone mineral status in children with Marfan syndrome
    journal, August 2012

    • Grover, Monica; Brunetti‐Pierri, Nicola; Belmont, John
    • American Journal of Medical Genetics Part A, Vol. 158A, Issue 9
    • DOI: 10.1002/ajmg.a.35540

    The TGF-β signalling negative regulator PICK1 represses prostate cancer metastasis to bone
    journal, July 2017

    • Dai, Yuhu; Ren, Dong; Yang, Qing
    • British Journal of Cancer, Vol. 117, Issue 5
    • DOI: 10.1038/bjc.2017.212

    TGFβ-Mediated induction of SphK1 as a potential determinant in human MDA-MB-231 breast cancer cell bone metastasis
    journal, July 2015

    Differential stem- and progenitor-cell trafficking by prostaglandin E2
    journal, March 2013

    • Hoggatt, Jonathan; Mohammad, Khalid S.; Singh, Pratibha
    • Nature, Vol. 495, Issue 7441
    • DOI: 10.1038/nature11929

    Excess TGF-β mediates muscle weakness associated with bone metastases in mice
    journal, October 2015

    • Waning, David L.; Mohammad, Khalid S.; Reiken, Steven
    • Nature Medicine, Vol. 21, Issue 11
    • DOI: 10.1038/nm.3961

    Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity
    journal, June 2018

    • Asparuhova, Maria B.; Caballé-Serrano, Jordi; Buser, Daniel
    • International Journal of Oral Science, Vol. 10, Issue 2
    • DOI: 10.1038/s41368-018-0021-2

    Targeting the Transforming Growth Factor-β pathway inhibits human basal-like breast cancer metastasis
    journal, January 2010

    Hypoxia and TGF-β Drive Breast Cancer Bone Metastases through Parallel Signaling Pathways in Tumor Cells and the Bone Microenvironment
    journal, September 2009

    TGF-β Inhibition Restores Terminal Osteoblast Differentiation to Suppress Myeloma Growth
    journal, March 2010

    TGF-β1 As Possible Link between Loss of Bone Mineral Density and Chronic Inflammation
    journal, November 2010

    Anti-Transforming Growth Factor ß Antibody Treatment Rescues Bone Loss and Prevents Breast Cancer Metastasis to Bone
    journal, November 2011

    Low Bone Turnover and Low BMD in Down Syndrome: Effect of Intermittent PTH Treatment
    journal, August 2012

    Load Regulates Bone Formation and Sclerostin Expression through a TGFβ-Dependent Mechanism
    journal, January 2013

    TGF-Beta Negatively Regulates the BMP2-Dependent Early Commitment of Periodontal Ligament Cells into Hard Tissue Forming Cells
    journal, May 2015

    Enhanced Bone Metastases in Skeletally Immature Mice
    journal, June 2018

    Osteolytic Breast Cancer Causes Skeletal Muscle Weakness in an Immunocompetent Syngeneic Mouse Model
    journal, December 2017

    TGF-Beta Signaling in Bone with Chronic Kidney Disease
    journal, August 2018

    • Iwasaki, Yoshiko; Yamato, Hideyuki; Fukagawa, Masafumi
    • International Journal of Molecular Sciences, Vol. 19, Issue 8
    • DOI: 10.3390/ijms19082352

    TGF-β Signaling in Bone Remodeling and Osteosarcoma Progression
    journal, November 2016

    • Lamora, Audrey; Talbot, Julie; Mullard, Mathilde
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    The Effect of Exogenous Zinc Concentration on the Responsiveness of MC3T3-E1 Pre-Osteoblasts to Surface Microtopography: Part II (Differentiation)
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    • Dorst, Kathryn; Rammelkamp, Derek; Hadjiargyrou, Michael
    • Materials, Vol. 7, Issue 2
    • DOI: 10.3390/ma7021097

    miR‑203‑3p participates in the suppression of diabetes‑associated osteogenesis in the jaw bone through targeting Smad1
    journal, January 2018

    • Tang, Yuying; Zheng, Leilei; Zhou, Jie
    • International Journal of Molecular Medicine
    • DOI: 10.3892/ijmm.2018.3373

    Bisphosphonate Modulation of the Gene Expression of Different Markers Involved in Osteoblast Physiology: Possible Implications in Bisphosphonate-Related Osteonecrosis of the Jaw
    journal, January 2018

    • Manzano-Moreno, Francisco Javier; Ramos-Torrecillas, Javier; Melguizo-Rodríguez, Lucia
    • International Journal of Medical Sciences, Vol. 15, Issue 4
    • DOI: 10.7150/ijms.22627
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