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Bone Morphogenetic Proteins and Other Bone Growth Factors

  • Chapter
Musculoskeletal Tissue Regeneration

Part of the book series: Orthopedic Biology and Medicine ((OBM))

  • 1766 Accesses

Abstract

Dr. Marshall Urist's discovery of the osteoinductive properties of bone morphogenetic proteins (BMPs) nearly 40 years ago marked the beginning of a new era in bone biology that has bridged the gap from bench to bedside. BMPs have the potential to greatly advance the fi elds of orthopaedic, oral/maxillofacial and craniofacial plastic surgery, as well as dentistry. Numerous BMPs have now been identified; of these, recombinant human BMP-2 and BMP-7 (OP-1) are the best characterized. These BMPs exert their effects via serine/threonine receptor-activated Smad signaling. Mutations that alter BMP regulation at the cellular level have been shown to result in various skeletal disorders. Animal studies in which BMPs are tested in sites that would otherwise not support bone formation have demonstrated the osteoinductive properties of several of the BMPs, and studies assessing the use of BMPs in orthotopic sites have provided great insight into optimal BMP delivery methods. Currently, BMP-2 and BMP-7 are approved for specifi c human orthopaedic applications. It is becoming clear that clinical use of BMPs requires application-specifi c testing to determine correct dosing and delivery kinetics. Autologous growth and angiogenic factors are also being explored for use in orthopaedics and will also likely play important roles in enhancing BMP delivery. Long-term effects, especially in developing bone, will need to be probed before BMP treatment can be expanded to more general clinical use. Bone morphogenetic proteins have great clinical potential; however, further investigations into their applied biology are necessary for safe and effective therapeutic applications.

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References

  1. 1. Urist MR. Bone: formation by autoinduction. Science 1965;150(698):893–9.

    Article  PubMed  CAS  Google Scholar 

  2. 2. Urist MR, Mikulski AJ, Nakagawa M, Yen K. A bone matrix calcification-initiator noncollagenous protein. Am J Physiol 1977;232(3):C115–27.

    PubMed  CAS  Google Scholar 

  3. 3. Urist MR, Lietze A, Mizutani H, et al. A bovine low molecular weight bone morphogenetic protein (BMP) fraction. Clin Orthop Relat Res 1982(162):219–32.

    Google Scholar 

  4. 4. Wozney JM, Rosen V, Celeste AJ, et al. Novel regulators of bone formation: molecular clones and activities. Science 1988;242(4885):1528–34.

    Article  PubMed  CAS  Google Scholar 

  5. 5. Wozney JM. The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev 1992;32(2):160–7.

    Article  PubMed  CAS  Google Scholar 

  6. 6. Wozney JM. Bone morphogenetic proteins. Prog Growth Factor Res 1989;1(4):267–80.

    Article  PubMed  CAS  Google Scholar 

  7. 7. Reddi AH. Bone and cartilage differentiation. Curr Opin Genet Dev 1994;4(5):737–44.

    Article  PubMed  CAS  Google Scholar 

  8. 8. Chen D, Zhao M, Mundy GR. Bone morphogenetic proteins. Growth Factors 2004;22(4):233–41.

    Article  PubMed  CAS  Google Scholar 

  9. 9. Scheufler C, Sebald W, Hulsmeyer M. Crystal structure of human bone morphogenetic protein-2 at 2.7 A resolution. J Mol Biol 1999;287(1):103–15.

    Article  PubMed  CAS  Google Scholar 

  10. 10. Shimell MJ, Ferguson EL, Childs SR, O'Connor MB. The Drosophila dorsalventral patterning gene tolloid is related to human bone morphogenetic protein 1. Cell 1991;67(3):469–81.

    Article  PubMed  CAS  Google Scholar 

  11. 11. Sampath TK, Muthukumaran N, Reddi AH. Isolation of osteogenin, an extracellular matrix-associated, bone-inductive protein, by heparin affinity chromatography. Proc Natl Acad Sci U S A 1987;84(20):7109–13.

    Article  PubMed  CAS  Google Scholar 

  12. 12. Ozkaynak E, Rueger DC, Drier EA, et al. OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. Embo J 1990;9(7):2085–93.

    PubMed  CAS  Google Scholar 

  13. 13. Sampath TK, Coughlin JE, Whetstone RM, et al. Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. J Biol Chem 1990;265(22):13198–205.

    PubMed  CAS  Google Scholar 

  14. 14. Koenig BB, Cook JS, Wolsing DH, et al. Characterization and cloning of a receptor for BMP-2 and BMP-4 from NIH 3T3 cells. Mol Cell Biol 1994;14(9):5961–74.

    PubMed  CAS  Google Scholar 

  15. 15. Moustakas A, Heldin CH. From mono- to oligo-Smads: the heart of the matter in TGF-beta signal transduction. Genes Dev 2002;16(15):1867–71.

    Article  PubMed  CAS  Google Scholar 

  16. 16. Chen Y, Bhushan A, Vale W. Smad8 mediates the signaling of the ALK-2 [corrected] receptor serine kinase. Proc Natl Acad Sci U S A 1997;94(24):12938–43.

    Article  PubMed  CAS  Google Scholar 

  17. 17. Zhao M, Qiao M, Oyajobi BO, Mundy GR, Chen D. E3 ubiquitin ligase Smurf1 mediates core-binding factor alpha1/Runx2 degradation and plays a specific role in osteoblast differentiation. J Biol Chem 2003;278(30):27939–44.

    Article  PubMed  CAS  Google Scholar 

  18. 18. Reddi AH. Interplay between bone morphogenetic proteins and cognate binding proteins in bone and cartilage development: noggin, chordin and DAN. Arthritis Res 2001;3(1):1–5.

    Article  PubMed  CAS  Google Scholar 

  19. 19. Wrana JL, Attisano L. The Smad pathway. Cytokine Growth Factor Rev 2000;11(1–2):5–13.

    Article  PubMed  CAS  Google Scholar 

  20. 20. Ebisawa T, Fukuchi M, Murakami G, et al. Smurf1 interacts with transforming growth factor-beta type I receptor through Smad7 and induces receptor degradation. J Biol Chem 2001;276(16):12477–80.

    Article  PubMed  CAS  Google Scholar 

  21. 21. 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(6):924–34.

    PubMed  CAS  Google Scholar 

  22. 22. Horiki M, Imamura T, Okamoto M, et al. Smad6/Smurf1 overexpression in cartilage delays chondrocyte hypertrophy and causes dwarfism with osteopenia. J Cell Biol 2004;165(3):433–45.

    Article  PubMed  CAS  Google Scholar 

  23. 23. 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(6):805–14.

    Article  PubMed  Google Scholar 

  24. 24. Yeomans JD, Urist MR. Bone induction by decalcified dentine implanted into oral, osseous and muscle tissues. Arch Oral Biol 1967;12(8):999–1008.

    Article  PubMed  CAS  Google Scholar 

  25. 25. Urist MR, Jurist JM, Jr., Dubuc FL, Strates BS. Quantitation of new bone formation in intramuscular implants of bone matrix in rabbits. Clin Orthop Relat Res 1970;68:279–93.

    Article  PubMed  CAS  Google Scholar 

  26. 26. Huggins C, Wiseman S, Reddi AH. Transformation of fibroblasts by allogeneic and xenogeneic transplants of demineralized tooth and bone. J Exp Med 1970;132(6):1250–8.

    Article  PubMed  CAS  Google Scholar 

  27. 27. Reddi AH, Huggins C. Biochemical sequences in the transformation of normal fibroblasts in adolescent rats. Proc Natl Acad Sci U S A 1972;69(6):1601–5.

    Article  PubMed  CAS  Google Scholar 

  28. 28. Carnes DL, Jr., De La Fontaine J, Cochran DL, et al. Evaluation of 2 novel approaches for assessing the ability of demineralized freeze-dried bone allograft to induce new bone formation. J Periodontol 1999;70(4):353–63.

    Article  PubMed  Google Scholar 

  29. 29. Helm GA, Sheehan JM, Sheehan JP, et al. Utilization of type I collagen gel, demineralized bone matrix, and bone morphogenetic protein-2 to enhance autologous bone lumbar spinal fusion. J Neurosurg 1997;86(1):93–100.

    Article  PubMed  CAS  Google Scholar 

  30. 30. Urist MR, Nilsson O, Rasmussen J, et al. Bone regeneration under the influence of a bone morphogenetic protein (BMP) beta tricalcium phosphate (TCP) composite in skull trephine defects in dogs. Clin Orthop Relat Res 1987(214):295–304.

    Google Scholar 

  31. 31. Johnson EE, Urist MR, Finerman GA. Resistant nonunions and partial or complete segmental defects of long bones. Treatment with implants of a composite of human bone morphogenetic protein (BMP) and autolyzed, antigen-extracted, allogeneic (AAA) bone. Clin Orthop Relat Res 1992(277):229–37.

    Google Scholar 

  32. 32. Heckman JD, Ingram AJ, Loyd RD, Luck JV, Jr., Mayer PW. Nonunion treatment with pulsed electromagnetic fields. Clin Orthop Relat Res 1981(161):58–66.

    Google Scholar 

  33. 33. Heckman JD, Ehler W, Brooks BP, et al. Bone morphogenetic protein but not transforming growth factor-beta enhances bone formation in canine diaphyseal nonunions implanted with a biodegradable composite polymer. J Bone Joint Surg Am 1999;81(12):1717–29.

    PubMed  CAS  Google Scholar 

  34. 34. Reddi AH, Cunningham NS. Initiation and promotion of bone differentiation by bone morphogenetic proteins. J Bone Miner Res 1993;8 Suppl 2:S499–502.

    PubMed  Google Scholar 

  35. 35. Boyan BD, Lohmann CH, Somers A, et al. Potential of porous poly-D,L-lactide-co-glycolide particles as a carrier for recombinant human bone morphogenetic protein-2 during osteoinduction in vivo. J Biomed Mater Res 1999;46(1):51–9.

    Article  PubMed  CAS  Google Scholar 

  36. 36. Ogawa Y, Schmidt DK, Nathan RM, et al. Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. J Biol Chem 1992;267(20):14233–7.

    PubMed  CAS  Google Scholar 

  37. 37. Sampath TK, Maliakal JC, Hauschka PV, et al. Recombinant human osteogenic protein-1 (hOP-1) induces new bone formation in vivo with a specific activity comparable with natural bovine osteogenic protein and stimulates osteoblast proliferation and differentiation in vitro. J Biol Chem 1992;267(28):20352–62.

    PubMed  CAS  Google Scholar 

  38. 38. Hotz G, Herr G. Bone substitute with osteoinductive biomaterials–current and future clinical applications. Int J Oral Maxillofac Surg 1994;23(6 Pt 2):413–7.

    Article  PubMed  CAS  Google Scholar 

  39. 39. Nakashima M. Induction of dentine in amputated pulp of dogs by recombinant human bone morphogenetic proteins−2 and −4 with collagen matrix. Arch Oral Biol 1994;39(12):1085–9.

    Article  PubMed  CAS  Google Scholar 

  40. 40. Rutherford B, Fitzgerald M. A new biological approach to vital pulp therapy. Crit Rev Oral Biol Med 1995;6(3):218–29.

    Article  PubMed  CAS  Google Scholar 

  41. 41. Rutherford B, Spangberg L, Tucker M, Charette M. Transdentinal stimulation of reparative dentine formation by osteogenic protein-1 in monkeys. Arch Oral Biol 1995;40(7):681–3.

    Article  PubMed  CAS  Google Scholar 

  42. 42. Rutherford RB, Wahle J, Tucker M, Rueger D, Charette M. Induction of reparative dentine formation in monkeys by recombinant human osteogenic protein-1. Arch Oral Biol 1993;38(7):571–6.

    Article  PubMed  CAS  Google Scholar 

  43. 43. Six N, Lasfargues JJ, Goldberg M. Differential repair responses in the coronal and radicular areas of the exposed rat molar pulp induced by recombinant human bone morphogenetic protein 7 (osteogenic protein 1). Arch Oral Biol 2002;47(3):177–87.

    Article  PubMed  CAS  Google Scholar 

  44. 44. Lieberman JR, Le LQ, Wu L, et al. Regional gene therapy with a BMP-2-produc- ing murine stromal cell line induces heterotopic and orthotopic bone formation in rodents. J Orthop Res 1998;16(3):330–9.

    Article  PubMed  CAS  Google Scholar 

  45. 45. Musgrave DS, Bosch P, Ghivizzani S, Robbins PD, Evans CH, Huard J. Adenovirusmediated direct gene therapy with bone morphogenetic protein-2 produces bone. Bone 1999;24(6):541–7.

    Article  PubMed  CAS  Google Scholar 

  46. 46. Riew KD, Wright NM, Cheng S, Avioli LV, Lou J. Induction of bone formation using a recombinant adenoviral vector carrying the human BMP-2 gene in a rabbit spinal fusion model. Calcif Tissue Int 1998;63(4):357–60.

    Article  PubMed  CAS  Google Scholar 

  47. 47. Kawai M, Bessho K, Maruyama H, Miyazaki J, Yamamoto T. Simultaneous gene transfer of bone morphogenetic protein (BMP) -2 and BMP-7 by in vivo electroporation induces rapid bone formation and BMP-4 expression. BMC Musculoskelet Disord 2006;7:62.

    Article  PubMed  Google Scholar 

  48. 48. Cook SD. Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 1999;22(7):669–71.

    PubMed  CAS  Google Scholar 

  49. 49. Friedlaender GE, Perry CR, Cole JD, et al. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am 2001;83-A Suppl 1(Pt 2):S151–8.

    PubMed  Google Scholar 

  50. 50. Boyan BD, Caplan AI, Heckman JD, Lennon DP, Ehler W, Schwartz Z. Osteochondral progenitor cells in acute and chronic canine nonunions. J Orthop Res 1999;17(2):246–55.

    Article  PubMed  CAS  Google Scholar 

  51. Syftestad GT, Urist MR. Bone aging. Clin Orthop Relat Res 1982(162):288–97.

    Google Scholar 

  52. 52. Schwartz Z, Somers A, Mellonig JT, et al. Ability of commercial demineralized freeze-dried bone allograft to induce new bone formation is dependent on donor age but not gender. J Periodontol 1998;69(4):470–8.

    PubMed  CAS  Google Scholar 

  53. 53. Honsawek S, Powers RM, Wolfinbarger L. Extractable bone morphogenetic protein and correlation with induced new bone formation in an in vivo assay in the athymic mouse model. Cell Tissue Bank 2005;6(1):13–23.

    Article  PubMed  CAS  Google Scholar 

  54. 54. Srouji S, Livne E. Bone marrow stem cells and biological scaffold for bone repair in aging and disease. Mech Ageing Dev 2005;126(2):281–7.

    Article  PubMed  CAS  Google Scholar 

  55. 55. Knutsen R, Wergedal JE, Sampath TK, Baylink DJ, Mohan S. Osteogenic protein-1 stimulates proliferation and differentiation of human bone cells in vitro. Biochem Biophys Res Commun 1993;194(3):1352–8.

    Article  PubMed  CAS  Google Scholar 

  56. 56. Burkus JK, Heim SE, Gornet MF, Zdeblick TA. Is INFUSE bone graft superior to autograft bone? An integrated analysis of clinical trials using the LT-CAGE lumbar tapered fusion device. J Spinal Disord Tech 2003;16(2):113–22.

    PubMed  Google Scholar 

  57. 57. Burkus JK, Sandhu HS, Gornet MF, Longley MC. Use of rhBMP-2 in combination with structural cortical allografts: clinical and radiographic outcomes in anterior lumbar spinal surgery. J Bone Joint Surg Am 2005;87(6):1205–12.

    Article  PubMed  Google Scholar 

  58. 58. Pradhan BB, Bae HW, Dawson EG, Patel VV, Delamarter RB. Graft resorption with the use of bone morphogenetic protein: lessons from anterior lumbar interbody fusion using femoral ring allografts and recombinant human bone morphogenetic protein-2. Spine 2006;31(10):E277–84.

    Article  PubMed  Google Scholar 

  59. 59. Baskin DS, Ryan P, Sonntag V, Westmark R, Widmayer MA. A prospective, randomized, controlled cervical fusion study using recombinant human bone morphogenetic protein-2 with the CORNERSTONE-SR allograft ring and the ATLANTIS anterior cervical plate. Spine 2003;28(12):1219–25; discussion 25.

    Article  PubMed  Google Scholar 

  60. 60. Boakye M, Mummaneni PV, Garrett M, Rodts G, Haid R. Anterior cervical discectomy and fusion involving a polyetheretherketone spacer and bone morphogenetic protein. J Neurosurg Spine 2005;2(5):521–5.

    Article  PubMed  Google Scholar 

  61. 61. Shields LB, Raque GH, Glassman SD, et al. Adverse effects associated with high-dose recombinant human bone morphogenetic protein-2 use in anterior cervical spine fusion. Spine 2006;31(5):542–7.

    Article  PubMed  Google Scholar 

  62. 62. 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(5):527–38; discussion 38–9.

    Article  PubMed  Google Scholar 

  63. Schwender JD, Holly LT, Rouben DP, Foley KT. Minimally invasive transforaminal lumbar interbody fusion (TLIF): technical feasibility and initial results. J Spinal Disord Tech 2005;18 Suppl:S1–6.

    Google Scholar 

  64. 64. Villavicencio AT, Burneikiene S, Nelson EL, Bulsara KR, Favors M, Thramann J. Safety of transforaminal lumbar interbody fusion and intervertebral recombinant human bone morphogenetic protein-2. J Neurosurg Spine 2005;3(6):436–43.

    Article  PubMed  Google Scholar 

  65. 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(24):2709–16.

    Article  PubMed  Google Scholar 

  66. 66. Vaccaro AR, Patel T, Fischgrund J, et al. A 2-year follow-up pilot study evaluating the safety and efficacy of op-1 putty (rhbmp-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. Eur Spine J 2005;14(7):623–9.

    Article  PubMed  Google Scholar 

  67. 67. Vaccaro AR, Patel T, Fischgrund J, et al. A pilot study evaluating the safety and efficacy of OP-1 Putty (rhBMP-7) as a replacement for iliac crest autograft in posterolateral lumbar arthrodesis for degenerative spondylolisthesis. Spine 2004;29(17):1885–92.

    Article  PubMed  Google Scholar 

  68. 68. Kanayama M, Hashimoto T, Shigenobu K, Yamane S, Bauer TW, Togawa D. A prospective randomized study of posterolateral lumbar fusion using osteogenic protein-1 (OP-1) versus local autograft with ceramic bone substitute: emphasis of surgical exploration and histologic assessment. Spine 2006;31(10):1067–74.

    Article  PubMed  Google Scholar 

  69. 69. Glassman SD, Dimar JR, Carreon LY, Campbell MJ, Puno RM, Johnson JR. Initial fusion rates with recombinant human bone morphogenetic protein-2/compression resistant matrix and a hydroxyapatite and tricalcium phosphate/collagen carrier in posterolateral spinal fusion. Spine 2005;30(15):1694–8.

    Article  PubMed  Google Scholar 

  70. 70. Singh K, Smucker JD, Boden SD. Use of recombinant human bone morphogenetic protein-2 as an adjunct in posterolateral lumbar spine fusion: a prospective CT-scan analysis at one and two years. J Spinal Disord Tech 2006;19(6):416–23.

    Article  PubMed  Google Scholar 

  71. 71. Luhmann SJ, Bridwell KH, Cheng I, Imamura T, Lenke LG, Schootman M. Use of bone morphogenetic protein-2 for adult spinal deformity. Spine 2005;30(17 Suppl): S110–7.

    Article  PubMed  Google Scholar 

  72. 72. 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-A(12):2123–34.

    PubMed  Google Scholar 

  73. 73. 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(6):1258–65.

    Article  PubMed  Google Scholar 

  74. 74. 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(7):1431–41.

    Article  PubMed  Google Scholar 

  75. McKee MD, Schemirsch EH, Waddel JP, et al. The effect of human recombinant bone morphogenic protein (rhBMP-7) on the healing of open tibial shaft fractures: results of a multi-center, prospective, randomized clinical trial. In: Orthopaedic Tramua Association, Paper #45; 2002; 2002.

    Google Scholar 

  76. Cole JD, Nguyen S. Review of healing with rhBMP-2/ACS use in the Medicare-aged population. In: Orthopaedic Trauma Association, Poster #102; 2006; 2006.

    Google Scholar 

  77. Hicks BD. BMP-2 and its use in nonunions and malunions. In: Orthopaedic Trauma Association, Poster #27; 2006; 2006.

    Google Scholar 

  78. Jones CB, Ringler JR, Enders TJ. Clinical outcomes for long-bone nonunions implanted with bone morphogenetic protein. In: Orthopaedic Trauma Association, Poster #30; 2006; 2006.

    Google Scholar 

  79. 79. Hu ZM, Peel SA, Sandor GK, Clokie CM. The osteoinductive activity of bone morphogenetic protein (BMP) purified by repeated extracts of bovine bone. Growth Factors 2004;22(1):29–33.

    Article  PubMed  CAS  Google Scholar 

  80. Kay JF, Khaliq SK, King E, Murray SS, Brochman EJ. Amounts of BMP-2, BMP-4, BMP-7 and TGF-B1 contained in DBM particles and DBM extract. In: Orthopaedic Research Society, Paper #1724; 2006; 2006.

    Google Scholar 

  81. 81. Carano RA, Filvaroff EH. Angiogenesis and bone repair. Drug Discov Today 2003;8(21):980–9.

    Article  PubMed  CAS  Google Scholar 

  82. 82. Simpson AH, Mills L, Noble B. The role of growth factors and related agents in accelerating fracture healing. J Bone Joint Surg Br 2006;88(6):701–5.

    Article  PubMed  CAS  Google Scholar 

  83. 83. Zhang Z, Lu S, Wang J. [Distribution and effectiveness of endogenic bone morphogenetic protein (BMP) in bone defect]. Zhonghua Wai Ke Za Zhi 1996;34(10):596–8.

    PubMed  CAS  Google Scholar 

  84. 84. Grageda E. Platelet-rich plasma and bone graft materials: a review and a standardized research protocol. Implant Dent 2004;13(4):301–9.

    PubMed  Google Scholar 

  85. 85. Roukis TS, Zgonis T, Tiernan B. Autologous platelet-rich plasma for wound and osseous healing: a review of the literature and commercially available products. Adv Ther 2006;23(2):218–37.

    Article  PubMed  Google Scholar 

  86. 86. Ranly DM, McMillan J, Keller T, et al. Platelet-derived growth factor inhibits demineralized bone matrix-induced intramuscular cartilage and bone formation. A study of immunocompromised mice. J Bone Joint Surg Am 2005;87(9):2052–64.

    Article  PubMed  Google Scholar 

  87. 87. Thorwarth M, Wehrhan F, Schultze-Mosgau S, Wiltfang J, Schlegel KA. PRP modulates expression of bone matrix proteins in vivo without long-term effects on bone formation. Bone 2006;38(1):30–40.

    Article  PubMed  CAS  Google Scholar 

  88. 88. Gruber R, Kandler B, Fischer MB, Watzek G. Osteogenic differentiation induced by bone morphogenetic proteins can be suppressed by platelet-released supernatant in vitro. Clin Oral Implants Res 2006;17(2):188–93.

    Article  PubMed  Google Scholar 

  89. Rai B, Oest ME, Dupont KM, Ho KH, Teoh SH, Guldberg RE. Combination of platelet-rich plasma with polycaprolactone-tricalcium phosphate scaffolds for segmental bone defect repair. J Biomed Mater Res A 2007.

    Google Scholar 

  90. 90. Sarkar MR, Augat P, Shefelbine SJ, et al. Bone formation in a long bone defect model using a platelet-rich plasma-loaded collagen scaffold. Biomaterials 2006;27(9):1817–23.

    Article  PubMed  CAS  Google Scholar 

  91. 91. Ranly DM, Lohmann CH, Andreacchio D, Boyan BD, Schwartz Z. Platelet-rich plasma inhibits demineralized bone matrix-induced bone formation in nude mice. J Bone Joint Surg Am 2007;89(1):139–47.

    Article  PubMed  Google Scholar 

  92. 92. Vladimirov BS, Dimitrov SA. Growth factors–importance and possibilities for enhancement of the healing process in bone fractures. Folia Med (Plovdiv) 2004;46(2):11–7.

    Google Scholar 

  93. 93. Chen CW, Tsai YH, Deng WP, et al. Type I and II collagen regulation of chondrogenic differentiation by mesenchymal progenitor cells. J Orthop Res 2005;23(2):446–53.

    Article  PubMed  CAS  Google Scholar 

  94. Hunziker EB, Driesang IM, Morris EA. Chondrogenesis in cartilage repair is induced by members of the transforming growth factor-beta superfamily. Clin Orthop Relat Res 2001(391 Suppl):S171–81.

    Google Scholar 

  95. 95. McGuire MK, Kao RT, Nevins M, Lynch SE. rhPDGF-BB promotes healing of periodontal defects: 24-month clinical and radiographic observations. Int J Periodontics Restorative Dent 2006;26(3):223–31.

    PubMed  Google Scholar 

  96. 96. Schmidt MB, Chen EH, Lynch SE. A review of the effects of insulin-like growth factor and platelet derived growth factor on in vivo cartilage healing and repair. Osteoarthritis Cartilage 2006;14(5):403–12.

    Article  PubMed  CAS  Google Scholar 

  97. 97. Coultas L, Chawengsaksophak K, Rossant J. Endothelial cells and VEGF in vascular development. Nature 2005;438(7070):937–45.

    Article  PubMed  CAS  Google Scholar 

  98. 98. Yancopoulos GD, Davis S, Gale NW, Rudge JS, Wiegand SJ, Holash J. Vascularspecific growth factors and blood vessel formation. Nature 2000;407(6801):242–8.

    Article  PubMed  CAS  Google Scholar 

  99. 99. Nakamae A, Sunagawa T, Ishida O, et al. Acceleration of surgical angiogenesis in necrotic bone with a single injection of fibroblast growth factor-2 (FGF-2). J Orthop Res 2004;22(3):509–13.

    Article  PubMed  CAS  Google Scholar 

  100. 100. Rabie AB, Lu M. Basic fibroblast growth factor up-regulates the expression of vascular endothelial growth factor during healing of allogeneic bone graft. Arch Oral Biol 2004;49(12):1025–33.

    Article  PubMed  CAS  Google Scholar 

  101. 101. Niedhart C, Maus U, Miltner O, Graber HG, Niethard FU, Siebert CH. The effect of basic fibroblast growth factor on bone regeneration when released from a novel in situ setting tricalcium phosphate cement. J Biomed Mater Res A 2004;69(4):680–5.

    Article  PubMed  Google Scholar 

  102. 102. Botta M, Manetti F, Corelli F. Fibroblast growth factors and their inhibitors. Curr Pharm Des 2000;6(18):1897–924.

    Article  PubMed  CAS  Google Scholar 

  103. 103. McKee MD, Nanci A. Osteopontin at mineralized tissue interfaces in bone, teeth, and osseointegrated implants: ultrastructural distribution and implications for mineralized tissue formation, turnover, and repair. Microsc Res Tech 1996;33(2):141–64.

    Article  PubMed  CAS  Google Scholar 

  104. 104. Green J, Schotland S, Stauber DJ, Kleeman CR, Clemens TL. Cell-matrix interaction in bone: type I collagen modulates signal transduction in osteoblast-like cells. Am J Physiol 1995;268(5 Pt 1):C1090–103.

    PubMed  CAS  Google Scholar 

  105. 105. Wang H, Li X, Tomin E, et al. Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis. J Orthop Res 2005;23(3):671–9.

    Article  PubMed  CAS  Google Scholar 

  106. 106. Bodamyali T, Bhatt B, Hughes FJ, et al. Pulsed electromagnetic fields simultaneously induce osteogenesis and upregulate transcription of bone morphogenetic proteins 2 and 4 in rat osteoblasts in vitro. Biochem Biophys Res Commun 1998;250(2):458–61.

    Article  PubMed  CAS  Google Scholar 

  107. 107. Lohmann CH, Schwartz Z, Liu Y, et al. Pulsed electromagnetic fields affect phenotype and connexin 43 protein expression in MLO-Y4 osteocyte-like cells and ROS 17/2.8 osteoblast-like cells. J Orthop Res 2003;21(2):326–34.

    Article  PubMed  CAS  Google Scholar 

  108. 108. Lohmann CH, Boyan BD, Simon BJ, Schwartz Z. Pulsed electromagnetic fields have direct effects on growth plate chondrocytes. Osteologie 2005;14(4):185–94.

    Article  Google Scholar 

  109. 109. Aaron RK, Ciombor DM. Acceleration of experimental endochondral ossification by biophysical stimulation of the progenitor cell pool. J Orthop Res 1996;14(4):582–9.

    Article  PubMed  CAS  Google Scholar 

  110. Aaron RK, Boyan BD, Ciombor DM, Schwartz Z, Simon BJ. Stimulation of growth factor synthesis by electric and electromagnetic fields. Clin Orthop Relat Res 2004(419):30–7.

    Google Scholar 

  111. 111. Harle J, Mayia F, Olsen I, Salih V. Effects of ultrasound on transforming growth factor-beta genes in bone cells. Eur Cell Mater 2005;10:70–6; discussion 6.

    PubMed  CAS  Google Scholar 

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Acknowledgments

The authors thank Professor Philip Boyne, Professor Emeritus, Loma Linda University, and Medtronic, Inc. for their generous gifts of graphics to support this paper. We acknowledge the support of Children's Healthcare of Atlanta, the Georgia Tech/Emory Center for the Engineering of Living Tissues, NIH, NSF and the Plastic Surgery Education Foundation for their support.

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Authors and Affiliations

  1. Institute of Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA, USA

    Barbara D. Boyan, Ramsey C. Kinney, Kimberly Singh & Zvi Schwartz

  2. Craniofacial Plastic Surgery, Children's Healthcare of Atlanta, Atlanta, GA, USA

    Joseph K. Williams

  3. Medtronic, Inc., Memphis, TN, USA

    Yolanda Cillo

  4. Hebrew University Hadassah Faculty of Dental Medicine, Jerusalem, Israel

    Zvi Schwartz

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  1. Barbara D. Boyan
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  2. Ramsey C. Kinney
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  3. Kimberly Singh
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  4. Joseph K. Williams
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  5. Yolanda Cillo
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  6. Zvi Schwartz
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Editors and Affiliations

  1. Department of Bioengineering, University of Illinois at Chicago, Chicago, IL, USA

    William S. Pietrzak Ph.D.

  2. Biomet, Inc., Warsaw, IN, USA

    William S. Pietrzak Ph.D.

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© 2008 Humana Press, a part of Springer Science+Business Media, LLC

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Boyan, B.D., Kinney, R.C., Singh, K., Williams, J.K., Cillo, Y., Schwartz, Z. (2008). Bone Morphogenetic Proteins and Other Bone Growth Factors. In: Pietrzak, W.S. (eds) Musculoskeletal Tissue Regeneration. Orthopedic Biology and Medicine. Humana Press. https://doi.org/10.1007/978-1-59745-239-7_11

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  • DOI: https://doi.org/10.1007/978-1-59745-239-7_11

  • Publisher Name: Humana Press

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