331
Views
36
CrossRef citations to date
0
Altmetric
Review

Targeting bone morphogenetic protein antagonists: in vitro and in vivo evidence of their role in bone metabolism

, MD, , MB ChB MRCS, , BSc(Hons), , MBBS MRCS, , MD, , MBBS MSc FDS FRCS & , MD MSc PhD FRCS show all
Pages 123-137 | Published online: 08 Dec 2008

Bibliography

  • Tsiridis E, Upadhyay N, Giannoudis P. Molecular aspects of fracture healing: which are important molecules? Injury 2007;38:11-25
  • Einhorn TA, Majeska RJ, Rush EB, et al. The expression of cytokine activity by fracture callus. J Bone Miner Res 1995;10:1272-81
  • Kloen P, Di Paola M, Borens O, et al. BMP signalling components are expressed in human fracture callus. Bone 2003;33:362-71
  • Bolander ME. Regulation of fracture repair by growth factors. Proc Soc Exp Biol Med 1992;200:165-70
  • Cho TJ, Gerstenfeld LC, Einhorn TA. Differential temporal expression of members of the transforming growth factor β superfamily during murine fracture healing. J Bone Miner Res 2002;17:513-20
  • Liu Z, Luyten FP, Lammens J, Dequeker J. Molecular signalling in bone fracture healing and distraction osteogenesis. Histol Histopathol 1999;14:587-95
  • Bostrom MP, Lane JM, Berberian WS, et al. Immunolocalization and expression of bone morphogenic proteins 2 and 4 in fracture healing. J Orthop Res 1995;13:357-67
  • Nakase T, Nomura S, Yoshikawa H, et al. Transient and localized expression of bone morphogenic protein 4 messenger RNA during fracture healing. J Bone Miner Res 1994;9:651-9
  • Onishi T, Ishidou Y, Nagamine T, et al. Distinct and overlapping patterns of localization of bone morphogenic protein (BMP) family members and a BMP type II receptor during fracture healing in rats. Bone 1998;22:605-12
  • Wozney JM, Rosen VM. Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. Clin Orthop Relat Res 1998;346:26-37
  • Reddi AH. Bone morphogenic proteins: from basic science to clinical applications. J Bone Joint Surg Am 2001;83:1-6
  • Sakou T, Onishi T, Yamamoto T, et al. Localization of Smads, the TGF-β family intracellular signalling components during endochondral ossification. J Bone Miner Res 1999;14:1145-52
  • Wozney JM, Rosen VM, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;242:1528-34
  • Nakayama K, Tamura Y, Suzawa M, et al. Receptor tyrosine kinases inhibit bone morphogenetic protein-Smad responsive promotor activity and differentiation of murine MC3T3-E1 osteoblast-like cells. J Bone Miner Res 2003;18:827-35
  • Urist MR. Bone: formation by autoinduction. Science 1965;150:893-9
  • Sampath TK, Muthukumaran N, Reddi AH. Isolation of osteogenin, an extracellular matrix-associated, bone-inductive protein, by heparin affinity chromatography. Proc Natl Acad Sci USA 1987;84:7109-13
  • Yanagita M. BMP antagonists: their roles in development and involvement in pathophysiology. Cytokine Growth Factor Rev 2005;16:309-17
  • Simic P, Vukicevic S. Bone morphogenetic proteins, from developmental signals to tissue regeneration. EMBO Rep 2007;8:327-31
  • Miyazono K, Maeda S, Imamura T. BMP receptor signalling: Transcriptional targets, regulation of signals, and signalling cross-talk. Cytokine Growth Factor Rev 2005;16:251-63
  • Canalis E, McCarthy TL, Centrella M. Effects of platelet-derived growth factor on bone formation in vitro J Cell Physiol 1989;140:530-7
  • Canalis E. Effect of platelet-derived growth factor on DNA and protein synthesis cultured in rat calvaria. Metabolism 1981;30:970-5
  • Buxton P, Edwards C, Archer CW, Francis-West P. Growth/differentiation factor-5 (GDF-5) and skeletal development. J Bone Joint Surg Am 2001;83:S23-30
  • Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22:233-41
  • Cheng H, Jiang W, Phillips FM, et al. Osteogenic activity of the fourteen types of human bone morphogenetic proteins (BMPs). J Bone Joint Surg Am 2003;85-A:1544-52
  • Yamada N, Kato M, Ten Dijke P, et al. Bone morphogenetic protein type IB receptor is progressively expressed in malignant glioma tumours. Br J Cancer 1996;73:624-9
  • Miyazono K. Signal transduction by bone morphogenetic protein: functional roles of Smad proteins. Bone 1999;25:91-3
  • Miyazono K, Maeda S, Imamura T. Endogenous TGF-β signalling suppresses maturation of osteoblastic mesenchymal cells. EMBO J 2004;23:552-63
  • Zhang YW, Yasui N, Ito K, et al. RUNX2/PEBP2aA/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia. Proc Natl Acad Sci USA 2000;97:10549-54
  • Groppe J, Greenwald J, Wiater E, et al. Structural basis of BMP inhibition by the cystine knot protein noggin. Nature 2002;420:636-42
  • Gazzerro E, Canalis E. Bone morphogenetic proteins and their antagonists. Rev Endocr Metab Disord 2006;7:51-65
  • Edgar CM, Chakravarthy V, Barnes G, et al. Autogenous regulation of a network of bone morphogenic proteins (BMP's) mediates the osteogenic differentiation in murine marrow stromal cells. Bone 2007;40:1389-98
  • Iwata T, Morotome Y, Tanabe T, et al. Noggin blocks osteoinductive activity of porcine enamel extracts. J Dent Res 2002;81:387-91
  • Van der Horst G, van Bezooijen RL, Deckers MM, et al. Differentiation of murine preosteoblastic KS483 cells depends on autocrine bone morphogenic protein signalling during all phases of osteoblast differentiation. Bone 2002;31(6):661-9
  • Wan DC, Pomerantz JH, Brunet LJ, et al. Noggin expression enhances in vitro osteogenesis and accelerates in vivo bone formation. J Biol Chem 2007;282:26450-9
  • Wu XB, Li Y, Schneider A, et al. Impaired osteoblastic differentiation, reduced bone formation, and severe osteoporosis in noggin-overexpressing mice. J Clin Invest 2003;112:924-34
  • Winkler DG, Yu C, Geoghegan JC, et al. Noggin and sclerostin bone morphogenic protein antagonists from a mutually inhibitory complex. J Biol Chem 2004;2779:36293-8
  • Devlin RD, Du Z, Pereira RC, et al. Skeletal overexpression of noggin results in osteopenia and reduced bone formation. Endocrinology 2003;144:1972-8
  • Petryk A, Shimmi O, Jia X, et al. Twisted gastrulation and chordin inhibit differentiation and mineralization in MC3T3-E1 osteoblast-like cells. Bone 2005;36:617-26
  • Chang C, Holtzman DA, Chau S, et al. Twisted gastrulation can function as a BMP antagonist. Nature 2001;410:483-7
  • Nosaka T, Morita S, Kitamura H, et al. Mammalian twisted gastrulation is essential for skeleto-lymphogenesis. Mol Cell Biol 2003;23:2969-80
  • Xie J, Fisher S. Twisted gastrulation enhances BMP signaling through chordin dependent and independent mechanisms. Development 2005;132:383-91
  • Oelgeschlager M, Larrain J, Geissert D, De Robertis EM. The evolutionarily conserved BMP-binding protein Twisted gastrulation promotes BMP signalling. Nature 2000;405:757-63
  • Ross JJ, Shimmi O, Vilmos P, et al. Twisted gastrulation is a conserved extracellular BMP antagonist. Nature 2001;410:479-83
  • Kwong FNK, Richardson SM, Evans CH. Chordin knockdown enhances the osteogenic differentiation of human mesenchymal stem cells. Arthritis Res Ther 2008;10(3):R65. Published online 4 June 2008, doi:10.1186/ar2436
  • Stein GS, Lian JB. Molecular mechanisms mediating proliferation/differentiation interrelationships during progressive development of the osteoblast phenotype. Endocr Rev 1993;14:424-42
  • Li X, Zhang Y, Kang H, et al. Sclerostin binds to LRP5/6 and antagonizes canonical Wnt signaling. J Biol Chem 2005;280:19883-7
  • ten Dijke P, Krause C, de Gorter DJ, et al. Osteocyte-derived sclerostin inhibits bone formation: its role in bone morphogenetic protein and Wnt signaling. J Bone Joint Surg Am 2008;90(Suppl 1):31-5
  • Pereira RC, Economides AN, Canalis E. Bone morphogenic proteins induce gremlin, a protein that limits their activity in osteoblasts. Endocrinology 2000;141:4558-63
  • Gazzero E, Pereira RC, Jorgetti V, et al. Skeletal over expression of gremlin impairs bone formation and causes osteopenia. Endocrinology 2005;146:655-65
  • Zanotti S, Smerdel-Ramoya A, Stadmeyer L, Canalis E. Activation of the ERK pathway in osteoblastic cells, role of gremlin and BMP-2. J Cell Biochem 2008;104:1421-6
  • Sutherland MK, Geoghegan JC, Yu C, et al. Sclerostin promotes the apoptosis of human osteoblastic cells: a novel regulation of bone formation. Bone 2004;35:828-35
  • Johnson ML, Kamel MA. The Wnt signaling pathway and bone metabolism. Curr Opin Rheumatol 2007;19:376-82
  • van Bezooijen RL, Roelen BA, Visser A, et al. Sclerostin is an osteocyte-expressed negative regulator of bone formation, but not a classical BMP antagonist. J Exp Med 2004;199:805-14
  • van Bezooijen RL, Svensson JP, Eefting D, et al. Wnt but not BMP signaling is involved in the inhibitory action of sclerostin on BMP-stimulated bone formation. J Bone Miner Res 2007;22:19-28
  • Li X, Ominsky MS, Niu QT, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008;23:860-9
  • Ishida W, Hamamoto T, Kusanagi K, et al. Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter. J Biol Chem 2000;275:6075-9
  • Fujii M, Takeda K, Imamura T, et al. Roles of bone morphogenic protein type I receptors and Smad proteins in osteoblast and chondroblast develpoment. Mol Cell Biol 1999;10:3801-13
  • Gazzerro E, Minetti C. Potential drug targets within bone morphogenetic protein signaling pathways. Curr Opin Pharmacol 2007;7:325-33
  • Ku M, Howard S, Ni W, et al. OAZ regulates bone morphogenetic protein signalling through Smad 6 activation. J Biol Chem 2006;281:5277-87
  • Mukai T, Otsuka F, Otani H, et al. TNF-α inhibits BMP-induced osteoblast differentiation through activating SAPK/JNK signalling. Biochem Biophys Res Commun 2007;356:1004-10
  • Hershko A, Ciechanover A. The ubiquitin system. Annu Rev Biochem 1998;67:425-79
  • Zhang Y, Chang C, Gehling DJ, et al. Regulation of Smad degradation and activity by Smurf2, an E3 ubiquitin ligase. Proc Natl Acad Sci USA 2001;98:974-9
  • Murakami G, Watabe T, Takaoka K, et al. Cooperative inhibition of bone morphogenetic protein signaling by Smurf1 and inhibitory Smads. Mol Biol Cell 2003;14:2809-17
  • Zhao M, Qiao M, Oyajobi BO, et al. E3 ubiquitin ligase Smurf1 mediates core-binding factor α1/Runx2 degradation and plays a specific role in osteoblast differentiation. J Biol Chem 2003;278:27939-44
  • Shen R, Chen M, Wang YJ, et al. Smad6 interacts with Runx2 and mediates Smad ubiquitin regulatory factor 1-induced Runx2 degradation. J Biol Chem 2006;281:3569-76
  • Kaneki H, Guo R, Chen D, et al. Tumor necrosis factor promotes Runx2 degradation through up-regulation of Smurf1 and Smurf2 in osteoblasts. J Biol Chem 2006;281:4326-33
  • Ying SX, Hussain ZJ, Zhang YE. Smurf1 facilitates myogenic differentiation and antagonizes the bone morphogenetic protein-2-induced osteoblast conversion by targeting Smad5 for degradation. J Biol Chem 2003;278:39029-36
  • Zhao M, Qiao M, Harris SE, et al. Smurf1 inhibits osteoblast differentiation and bone formation in vitro and in vivo J Biol Chem 2004;279:12854-9
  • Dupont S, Zacchigna L, Cordenonsi M, et al. Germ-layer specification and control of cell growth by Ectodermin, a Smad4 ubiquitin ligase. Cell 2005;121:87-99
  • Standal T, Abildgaard N, Fagerli UM, et al. HGF inhibits BMP-induced osteoblastogenesis: possible implications for the bone disease of multiple myeloma. Blood 2007;109:3024-30
  • Andersen NF, Standal T, Nielsen JL, et al. Syndecan-1 and angiogenic cytokines in multiple myeloma: correlation with bone marrow angiogenesis and survival. Br J Haematol 2005;128:210-7
  • Onichtchouk D, Chen YG, Dosch R, et al. Silencing of TGF-β signalling by the pseudoreceptor BAMBI. Nature 1999;401:480-5
  • Luo K. Negative regulation of BMP signaling by the ski oncoprotein. J Bone Joint Surg Am 2003;85-A(Suppl 3):39-43
  • Lehrmann H, Pritchard LL, Harel-Bellan A. Histone acetyltransferases and deacetylases in the control of cell proliferation and differentiation. Adv Cancer Res 2002;86:41-65
  • Horlein AJ, Naar AM, Heinzel T, et al. Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressor. Nature 1995;377:397-404
  • Wang W, Mariani FV, Harland RM, Luo K. Ski represses bone morphogenic protein signalling in Xenopus and mammalian cells. Proc Natl Acad Sci USA 2000;97:14394-9
  • Albertson KS, Medoff RJ, Mitsunaga MM. The use of periosteally vascularized autografts to augment the fixation of large segmental allografts. Clin Orthop Relat Res 1991;269:113-9
  • Enneking WF, Mindell ER. Observations on massive retrieved human allografts. J Bone Joint Surg Am 1991;73:1123-42
  • Southwood LL, Frisbie DD, Kawcak CE, et al. Evaluation of Ad-BMP-2 for enhancing fracture healing in an infected defect fracture rabbit model. J Orthop Res 2004;22:66-72
  • Helm GA, Dayoub H, Jane JA Jr. Bone graft substitutes for the promotion of spinal arthrodesis. Neurosurg Focus 2001;10(4):1-5
  • Bessa PC, Casal M, Reis RL. Bone morphogenetic proteins in tissue engineering: the road from laboratory to clinic, part II (BMP delivery). J Tissue Eng Regen Med 2008;2:81-96
  • Groeneveld EH, Burger EH. Bone morphogenetic proteins in human bone regenration. Eur J Endocrinol 2000;142:9-21
  • Einhorn TA. Clinical applications of recombinant human BMPs: early experience and future development. J Bone Joint Surg Am 2003;85:82-8
  • Dimar JR, Glassman SD, Burkus KJ, Carreon LY. Clinical outcomes and fusion success at 2 years of single-level instrumented posterolateral fusions with recombinant human bone morphogenetic protein-2/compression resistant matrix versus iliac crest bone graft. Spine 2006;31:2534-9; discussion 40
  • Govender S, Csimma C, Genant HK, et al. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 2002;84:2123-34
  • Haid RW Jr, Branch CL Jr, Alexander JT, Burkus JK. Posterior lumbar interbody fusion using recombinant human bone morphogenetic protein type 2 with cylindrical interbody cages. Spine J 2004;4:527-38; discussion 538-9
  • Jones AL, Bucholz RW, Bosse MJ, et al. Recombinant human BMP-2 and allograft compared with autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects. A randomized, controlled trial. J Bone Joint Surg Am 2006;88:1431-41
  • Swiontkowski MF, Aro HT, Donell S, et al. Recombinant human bone morphogenetic protein-2 in open tibial fractures. A subgroup analysis of data combined from two prospective randomized studies. J Bone Joint Surg Am 2006;88:1258-65
  • Vaccaro AR, Anderson DG, Patel T, et al. Comparison of OP-1 Putty (rhBMP-7) to iliac crest autograft for posterolateral lumbar arthrodesis: a minimum 2-year follow-up pilot study. Spine 2005;30:2709-16
  • Vaccaro AR, Whang PG, Patel T, et al. The safety and efficacy of OP-1 (rhBMP-7) as a replacement for iliac crest autograft for posterolateral lumbar arthrodesis: minimum 4-year follow-up of a pilot study. Spine J 2008;8:457-65
  • Franceschi RT. Biological approaches to bone regeneration by gene therapy. J Dent Res 2005;84:1093-03
  • Zhu W, Rawlins BA, Boachie-Adjei O, et al. Combined bone morphogenetic protein 2 and 7 gene transfer enhances osteoblastic differentiation and spine fusion in a rodent model. J Bone Miner Res 2004;19:2021-32
  • Abe E, Yamamoto M, Taguchi Y, et al. Essential requirement for BMP's 2/4 for both osteoblast and osteoclast formation in murine bone marrow cultures from adult mice: antagonism by noggin. J Bone Miner Res 2000;15:663-73
  • Valentin-Opran A, Wozney J, Csimma C, et al. Clinical evaluation of recombinant human bone morphogenetic protein-2. Clin Orthop Relat Res 2002;395:110-20
  • Heliotis M, Tsiridis E. Suppression of bone morphogenetic protein inhibitors promotes osteogenic differentiation: therapeutic implications. Arthritis Res Ther 2008;10:115. Published online 12 August 2008, doi:10.1186/ar2467
  • Oshima T, Abe M, Asano J, et al. Myeloma cells suppress bone formation by secreting a soluble Wnt inhibitor, sFRP-2. Blood 2005;106:3160-5
  • Chopra DP, Menard RE, Januszewski J, Mattingly RR. TNF-α-mediated apoptosis in normal human prostate epithelial cells and tumor cell lines. Cancer Lett 2004;203:145-54
  • Lakshmikanthan V, Kaddour-Djebbar I, Lewis RW, Kumar MV. SAHA-sensitized prostate cancer cells to TNFα-related apoptosis-inducing ligand (TRAIL): mechanisms leading to synergistic apoptosis. Int J Cancer 2006;119:221-8
  • Balemans W, Van Den Ende J, Freire Paes-Alves A, et al. Localization of the gene for sclerosteosis to the van Buchem disease-gene region on chromosome 17q12-q21. Am J Hum Genet 1999;64:1661-9
  • Gardner JC, van Bezooijen RL, Mervis B, et al. Bone mineral density in sclerosteosis; affected individuals and gene carriers. J Clin Endocrinol Metab 2005;90:6392-5
  • Ominsky M, Stouch B, Doellgast G, et al. Administration of sclerostin monoclonal antibodies to female cynomolgus monkeys result in increased bone formation, bone mineral density and bone strength [abstract]. J Bone Min Res 2006;21(Suppl 1):S44
  • Ominsky MS, Warmington KS, Asuncion FJ, et al. Sclerostin monoclonal antibody treatment increases bone strength in aged osteopenic ovariectomized rats [abstract]. J Bone Min Res 2006;21(Suppl 1):S44
  • Tsiridis E, Ali Z, Bhalla A, et al. In vitro and in vivo optimization of impaction allografting by demineralization and addition of rh-OP-1. J Orthop Res 2007;25:1425-37

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.