Stimulation of bone regeneration using bone morphogenetic proteins: modern concepts

封面


如何引用文章

全文:

开放存取 开放存取
受限制的访问 ##reader.subscriptionAccessGranted##
受限制的访问 订阅或者付费存取

详细

Restoration of fractures or bone defects after trauma is known to be one of the urgent problems of modern orthopedics and traumatology. More than 20 types of bone morphogenetic proteins create a part of transforming growth factor beta superfamily. It has been revealed that such types as BMP-2, -4, -6, -7 and -9 have the most pronounced osteogenic properties. They induce migration, proliferation and differentiation of mesenchymal stem cells to form osteoblasts and chondroblasts, as well as inductively influence various stages of the bone healing process such as angiogenesis, callus formation and bone remodeling. Some recombinant bone morphogenetic proteins, such as rhBMP-2 and rhBMP-7 approved for human clinical use by the Food and Drug Administration (FDA, USA) are used in combination with bone grafts to enhance reparative osteogenesis in the treatment of injuries. and replacement of bone defects in spinal surgery. Therefore, the use of the unique properties of these proteins has become one of the promising and rapidly developing areas of practical medicine. The article is devoted to the analysis of the most important concepts for using bone morphogenetic proteins to stimulate bone tissue regeneration.

全文:

受限制的访问

作者简介

Ural Mukhametov

G.G. Kuvatov Republican Clinical Hospital

Email: ufa.rkbkuv@doctorrb.ru
ORCID iD: 0000-0003-3694-3302

MD, Cand. Sci. (Med.)

俄罗斯联邦, 3 Lenin St., Ufa, 450008

Sergey Lyulin

Medical Center “Carmel”

Email: carmel74@yandex.ru
ORCID iD: 0000-0002-2549-1059
SPIN 代码: 4968-8680
Scopus 作者 ID: 6701421057
Researcher ID: M-8114-2013

MD, Dr. Sci. (Med.), Professor

俄罗斯联邦, Chelyabinsk

Dmitry Borzunov

Ural State Medical University

Email: borzunov@bk.ru
ORCID iD: 0000-0003-3720-5467
SPIN 代码: 6858-8005
Scopus 作者 ID: 17433431500

MD, Dr. Sci. (Med.), Professor

俄罗斯联邦, Ekaterinburg

Ilgiz Gareev

Bashkir State Medical University

编辑信件的主要联系方式.
Email: ilgiz_gareev@mail.ru
ORCID iD: 0000-0002-4965-0835
SPIN 代码: 3839-0621
Scopus 作者 ID: 57206481534

MD, PhD

俄罗斯联邦, 3 Lenin St., Ufa, 450008

参考

  1. Kolsanov AV, Suslin SA, Vavilov AV, et al. Prevention of time risks, medical and economic costs during planned hospitalization in a multidisciplinary hospital. Profilakticheskaya Meditsina. 2021;24(7):117–122. (In Russ.). doi: 10.17116/profmed202124071117
  2. Ananeva AS, Baraeva LM, Bykov IM, et al. Modeling of bone injuries in animal experiments. Innovative Medicine of Kuban. 2021;(1):47–55. (In Russ.). doi: 10.35401/2500-0268-2021-21-1-47-55
  3. Zhang Y, Ma J, Zhang W. Berberine for bone regeneration: Therapeutic potential and molecular mechanisms. J Ethnopharmacol. 2021;277:114249. doi: 10.1016/j.jep.2021.114249
  4. Bal Z, Kushioka J, Kodama J, et al. BMP and TGFbeta use and release in bone regeneration. Turk J Med Sci. 2020;50(SI–2):1707–1722. doi: 10.3906/sag-2003-127
  5. Sampath TK, Reddi AH. Discovery of bone morphogenetic proteins – A historical perspective. Bone. 2020;140:115548. doi: 10.1016/j.bone.2020.115548
  6. Wu Z, Zhou B, Chen L, et al. Bone morphogenetic protein-2 against iliac crest bone graft for the posterolateral fusion of the lumbar spine: A meta-analysis. Int J Clin Pract. 2021;75(4):e13911. doi: 10.1111/ijcp.13911
  7. Kuznetsova VS, Vasilyev AV, Bukharova TB, et al. Safety and efficacy of BMP-2 and BMP-7 use in dentistry. Stomatologiya (Mosk). 2019;98(1):64–69. (In Russ.). doi: 10.17116/stomat20199801164
  8. Bannwarth M, Smith JS, Bess S, et al. Use of rhBMP-2 for adult spinal deformity surgery: patterns of usage and changes over the past decade. Neurosurg Focus. 2021;50(6):E4. doi: 10.3171/2021.3.FOCUS2164
  9. Christian J. A tale of two receptors: Bmp heterodimers recruit two type I receptors but use the kinase activity of only one. Proc Natl Acad Sci USA. 2021;118(19):e2104745118. doi: 10.1073/pnas.2104745118
  10. Vassiliou AG, Keskinidou C, Kotanidou A, et al. Knockdown of bone morphogenetic protein type II receptor leads to decreased aquaporin 1 expression and function in human pulmonary microvascular endothelial cells. Can J Physiol Pharmacol. 2020;98(11):834–839. doi: 10.1139/cjpp-2020-0185
  11. Sun W, Li M, Zhang Y, et al. Total flavonoids of rhizoma drynariae ameliorates bone formation and mineralization in BMP-SMAD signaling pathway induced large tibial defect rats. Biomed Pharmacother. 2021;138:111480. doi: 10.1016/j.biopha.2021.111480
  12. Luo X, Chang HM, Yi Y, et al. Bone morphogenetic protein 2 upregulates SERPINE2 expression through noncanonical SMAD2/3 and p38 MAPK signaling pathways in human granulosa-lutein cells. FASEB J. 2021;35(9):e21845. doi: 10.1096/fj.202100670RR
  13. Osses N, Gutierrez J, Lopez-Rovira T, et al. Sulfation is required for bone morphogenetic protein 2-dependent Id1 induction. Biochem Biophys Res Commun. 2006;344(4):1207–1215. doi: 10.1016/j.bbrc.2006.04.029
  14. Zhao B, Katagiri T, Toyoda H, et al. Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2. J Biol Chem. 2006;281(32):23246–2353. doi: 10.1074/jbc.M511039200
  15. Zhou H, Qian J, Wang J, et al. Enhanced bioactivity of bone morphogenetic protein-2 with low dose of 2-N, 6-O-sulfated chitosan in vitro and in vivo. Biomaterials. 2009;30(9):1715–1724. doi: 10.1016/j.biomaterials.2008.12.016
  16. Chen R, Yu J, Gong HL, et al. An easy long-acting BMP7 release system based on biopolymer nanoparticles for inducing osteogenic differentiation of adipose mesenchymal stem cells. J Tissue Eng Regen Med. 2020;14(7):964–972. doi: 10.1002/term.3070
  17. Todd GM, Gao Z, Hyvönen M, et al. Secreted BMP antagonists and their role in cancer and bone metastases. Bone. 2020;137:115455. doi: 10.1016/j.bone.2020.115455
  18. Gao Y, Zhang M, Tian X, et al. Experimental animal study on BMP-3 expression in periodontal tissues in the process of orthodontic tooth movement. Exp Ther Med. 2019;17(1):193–198. doi: 10.3892/etm.2018.6950
  19. Iyer S, Pennisi DJ, Piper M. Crim1-, a regulator of developmental organogenesis. Histol Histopathol. 2016;31(10):1049–1057. doi: 10.14670/HH-11-766
  20. Zhao HJ, Chang HM, Klausen C, et al. Bone morphogenetic protein 2 induces the activation of WNT/beta-catenin signaling and human trophoblast invasion through up-regulating BAMBI. Cell Signal. 2020;67:109489. doi: 10.1016/j.cellsig.2019.109489
  21. Madhu V, Kilanski A, Reghu N, et al. Expression of CD105 and CD34 receptors controls BMP-induced in vitro mineralization of mouse adipose-derived stem cells but does not predict their in vivo bone-forming potential. J Orthop Res. 2015;33(5):625–632. doi: 10.1002/jor.22883
  22. Gomez-Puerto MC, Iyengar PV, García de Vinuesa A, et al. Bone morphogenetic protein receptor signal transduction in human disease. J Pathol. 2019;247(1):9–20. doi: 10.1002/path.5170
  23. El Bialy I, Jiskoot W, Reza Nejadnik M. Formulation, delivery and stability of bone morphogenetic proteins for effective bone regeneration. Pharm Res. 2017;34(6):1152–1170. doi: 10.1007/s11095-017-2147-x
  24. Engstrand T, Veltheim R, Arnander C, et al. A novel biodegradable delivery system for bone morphogenetic protein-2. Plast Reconstr Surg. 2008;121(6):1920–1928. doi: 10.1097/PRS.0b013e31817151b0
  25. Briquez PS, Tsai HM, Watkins EA, Hubbell JA. Engineered bridge protein with dual affinity for bone morphogenetic protein-2 and collagen enhances bone regeneration for spinal fusion. Sci Adv. 2021;7(24):eabh4302. doi: 10.1126/sciadv.abh4302
  26. Yang X, Han G, Pang X, Fan M. Chitosan/collagen scaffold containing bone morphogenetic protein-7 DNA supports dental pulp stem cell differentiation in vitro and in vivo. J Biomed Mater Res A. 2020;108(12):2519–2526. doi: 10.1002/jbm.a.34064
  27. Fischer J, Kolk A, Wolfart S, et al. Future of local bone regeneration – Protein versus gene therapy. J Craniomaxillofac Surg. 2011;39(1):54–64. doi: 10.1016/j.jcms.2010.03.016
  28. Mirmohseni F, Cheng T, Oveissi F, et al. Optimized synthesis of poly(deoxyribose) isobutyrate, a viscous biomaterial for bone morphogenetic protein-2 delivery. ACS Appl Mater Interfaces. 2019;11(3):2870–2879. doi: 10.1021/acsami.8b20126
  29. Carreira AC, Lojudice FH, Halcsik E, et al. Bone morphogenetic proteins: facts, challenges, and future perspectives. J Dent Res. 2014;93(4):335–345. doi: 10.1177/0022034513518561
  30. Chen R, Yu Y, Zhang W, et al. Tuning the bioactivity of bone morphogenetic protein-2 with surface immobilization strategies. Acta Biomater. 2018;80:108–120. doi: 10.1016/j.actbio.2018.09.011
  31. Wang J, Zhang H, Zhu X, et al. Dynamic competitive adsorption of bone-related proteins on calcium phosphate ceramic particles with different phase composition and microstructure. J Biomed Mater Res B Appl Biomater. 2013;101(6):1069–1077. doi: 10.1002/jbm.b.32917
  32. Shiels SM, Solomon KD, Pilia M, et al. BMP-2 tethered hydroxyapatite for bone tissue regeneration: Coating chemistry and osteoblast attachment. J Biomed Mater Res A. 2012;100(11):3117–3123. doi: 10.1002/jbm.a.34241
  33. Cheng CH, Lai YH, Chen YW, et al. Immobilization of bone morphogenetic protein-2 to gelatin/avidin-modified hydroxyapatite composite scaffolds for bone regeneration. J Biomater Appl. 2019;33(9):1147–1156. doi: 10.1177/0885328218820636
  34. Chien CY, Tsai WB. Poly(dopamine)-assisted immobilization of Arg-Gly-Asp peptides, hydroxyapatite, and bone morphogenic protein-2 on titanium to improve the osteogenesis of bone marrow stem cells. ACS Appl Mater Interfaces. 2013;5(15):6975–6983. doi: 10.1021/am401071f
  35. Ko E, Yang K, Shin J, Cho SW. Polydopamine-assisted osteoinductive peptide immobilization of polymer scaffolds for enhanced bone regeneration by human adipose-derived stem cells. Biomacromolecules. 2013;14(9):3202–3213. doi: 10.1021/bm4008343
  36. Ruhé PQ, Kroese-Deutman HC, Wolke JG, et al. Bone inductive properties of rhBMP-2 loaded porous calcium phosphate cement implants in cranial defects in rabbits. Biomaterials. 2004;25(11):2123–2132. doi: 10.1016/j.biomaterials.2003.09.007
  37. Zhao J, Shen G, Liu C, et al. Enhanced healing of rat calvarial defects with sulfated chitosan-coated calcium-deficient hydroxyapatite/bone morphogenetic protein 2 scaffolds. Tissue Eng Part A. 2012;18(1–2):185–197. doi: 10.1089/ten.TEA.2011.0297
  38. Kim MG, Kim CL, Kim YS, et al. Selective endocytosis of recombinant human BMP through cell surface heparan sulfate proteoglycans in CHO cells: BMP-2 and BMP-7. Sci Rep. 2021;11(1):3378. doi: 10.1038/s41598-021-82955-1
  39. Haubruck P, Tanner MC, Vlachopoulos W, et al. Comparison of the clinical effectiveness of Bone Morphogenic Protein (BMP) -2 and -7 in the adjunct treatment of lower limb nonunions. Orthop Traumatol Surg Res. 2018;104(8):1241–1248. doi: 10.1016/j.otsr.2018.08.008
  40. Teng F, Yu D, Wei L, et al. Preclinical application of recombinant human bone morphogenetic protein 2 on bone substitutes for vertical bone augmentation: A systematic review and meta-analysis. J Prosthet Dent. 2019;122(4):355–363. doi: 10.1016/j.prosdent.2018.09.008
  41. Nauth A, Schemitsch E, Norris B, et al. Critical-size bone defects: is there a consensus for diagnosis and treatment? J Orthop Trauma. 2018;32 Suppl 1:S7–S11. doi: 10.1097/BOT.0000000000001115
  42. Wikesjö UM, Polimeni G, Qahash M. Tissue engineering with recombinant human bone morphogenetic protein-2 for alveolar augmentation and oral implant osseointegration: experimental observations and clinical perspectives. Clin Implant Dent Relat Res. 2005;7(2):112–119. doi: 10.1111/j.1708-8208.2005.tb00054.x
  43. Long J, Li P, Du HM, et al. Effects of bone morphogenetic protein 2 gene therapy on new bone formation during mandibular distraction osteogenesis at rapid rate in rabbits. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;112(1):50–57. doi: 10.1016/j.tripleo.2010.09.065
  44. Turgeman G, Zilberman Y, Zhou S, et al. Systemically administered rhBMP-2 promotes msc activity and reverses bone and cartilage loss in osteopenic mice. J Cell Biochem. 2002;86(3):461–474. doi: 10.1002/jcb.10231
  45. Crasto GJ, Kartner N, Reznik N, et al. Controlled bone formation using ultrasound-triggered release of BMP-2 from liposomes. J Control Release. 2016;243:99–108. doi: 10.1016/j.jconrel.2016.09.032
  46. Smith DM, Afifi AM, Cooper GM, et al. BMP-2-based repair of large-scale calvarial defects in an experimental model: regenerative surgery in cranioplasty. J Craniofac Surg. 2008;19(5):1315–1322. doi: 10.1097/SCS.0b013e3181843369
  47. Kerzner B, Martin HL, Weiser M, et al. A Reliable and reproducible critical-sized segmental femoral defect model in rats stabilized with a custom external fixator. J Vis Exp. 2019;(145):10.3791/59206. doi: 10.3791/59206
  48. Liu F, Wells JW, Porter RM, et al. Interaction between living bone particles and rhBMP-2 in large segmental defect healing in the rat femur. J Orthop Res. 2016;34(12):2137–2145. doi: 10.1002/jor.23255
  49. Lee J, Decker JF, Polimeni G, et al. Evaluation of implants coated with rhBMP-2 using two different coating strategies: a critical-size supraalveolar peri-implant defect study in dogs. J Clin Periodontol. 2010;37(6):582–590. doi: 10.1111/j.1600-051X.2010.01557.x
  50. Ripamonti U, van den Heever B, Sampath TK, et al. Complete regeneration of bone in the baboon by recombinant human osteogenic protein-1 (hOP-1, bone morphogenetic protein-7). Growth Factors. 1996;13(3–4):273–289. doi: 10.3109/08977199609003228
  51. Vincentelli AF, Szadkowski M, Vardon D, et al. rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) in real world spine surgery. A phase IV, National, multicentre, retrospective study collecting data from patient medical files in French spinal centres. Orthop Traumatol Surg Res. 2019;105(6):1157–1163. doi: 10.1016/j.otsr.2019.04.023
  52. Baltzer AW, Ostapczuk MS, Stosch D, Granrath M. The use of recombinant human bone morphogenetic protein-2 for the treatment of a delayed union following femoral neck open-wedge osteotomy. Orthop Rev (Pavia). 2012;4(1):e4. doi: 10.4081/or.2012.e4
  53. Julka A, Shah AS, Miller BS. Inflammatory response to recombinant human bone morphogenetic protein-2 use in the treatment of a proximal humeral fracture: a case report. J Shoulder Elbow Surg. 2012;21(1):e12–16. doi: 10.1016/j.jse.2011.06.006
  54. Von Rüden C, Morgenstern M, Hierholzer C, et al. The missing effect of human recombinant Bone Morphogenetic Proteins BMP-2 and BMP-7 in surgical treatment of aseptic forearm nonunion. Injury. 2016;47(4):919–924. doi: 10.1016/j.injury.2015.11.038
  55. Murena L, Canton G, Vulcano E, et al. Treatment of humeral shaft aseptic nonunions in elderly patients with opposite structural allograft, BMP-7, and mesenchymal stem cells. Orthopedics. 2014;37(2):e201–e206. doi: 10.3928/01477447-20140124-26
  56. Ollivier M, Gay AM, Cerlier A, et al. Can we achieve bone healing using the diamond concept without bone grafting for recalcitrant tibial nonunions? Injury. 2015;46(7):1383–1388. doi: 10.1016/j.injury.2015.03.036
  57. Calori GM, Colombo M, Bucci M, et al. Clinical effectiveness of Osigraft in long-bones nonunions. Injury. 2015;46 Suppl 8:S55–S64. doi: 10.1016/S0020-1383(15)30056-5
  58. Durdevic D, Vlahovic T, Pehar S, et al. A novel autologous bone graft substitute comprised of rhBMP6 blood coagulum as carrier tested in a randomized and controlled Phase I trial in patients with distal radial fractures. Bone. 2020;140:115551. doi: 10.1016/j.bone.2020.115551
  59. 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(12):2123–2134. doi: 10.2106/00004623-200212000-00001
  60. Sudsakorn S, Bahadduri P, Fretland J, Lu C. 2020 FDA Drug-drug Interaction Guidance: A comparison analysis and action plan by pharmaceutical industrial scientists. Curr Drug Metab. 2020;21(6):403–426. doi: 10.2174/1389200221666200620210522
  61. 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):S151–158.
  62. McKee MD, Schemitsch EH, Waddell 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: Proceedings of the 18th Annual Meeting of the Orthopaedic Trauma Association; 2002 Oct 11-13, Toronto, ON, Canada [Internet]. Available from: www.hwbf.org/ota/am/ota02/otapa/OTA02745.htm. Accessed: Dec 9, 2009.
  63. Bong MR, Capla EL, Egol KA, et al. Osteogenic protein-1 (bone morphogenic protein-7) combined with various adjuncts in the treatment of humeral diaphyseal nonunions. Bull Hosp Jt Dis. 2005;63(1–2):20–23.
  64. Oryan A, Alidadi S, Moshiri A, Bigham-Sadegh A. Bone morphogenetic proteins: a powerful osteoinductive compound with non-negligible side effects and limitations. Biofactors. 2014;40(5):459–481. doi: 10.1002/biof.1177
  65. Kanjilal D, Cottrell JA. Bone morphogenetic proteins (BMP) and bone regeneration. Methods Mol Biol. 2019;1891:235–245. doi: 10.1007/978-1-4939-8904-1_17
  66. Jain A, Yeramaneni S, Kebaish KM, et al. Cost-utility analysis of rhBMP-2 use in adult spinal deformity surgery. Spine (Phila Pa 1976). 2020;45(14):1009–1015. doi: 10.1097/BRS.0000000000003442
  67. Krishnakumar GS, Roffi A, Reale D, et al. Clinical application of bone morphogenetic proteins for bone healing: a systematic review. Int Orthop. 2017;41(6):1073–1083. doi: 10.1007/s00264-017-3471-9
  68. Lochmann A, Nitzsche H, von Einem S, et al. The influence of covalently linked and free polyethylene glycol on the structural and release properties of rhBMP-2 loaded microspheres. J Control Release. 2010;147(1):92–100. doi: 10.1016/j.jconrel.2010.06.021
  69. Alam S, Ueki K, Nakagawa K, et al. Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2009;107(1):22–29. doi: 10.1016/j.tripleo.2008.06.025
  70. Summary of safety and effectiveness data. 2002. The InFUSE™ Bone Graft/LT-CAGE™ Lumbar Tapered Fusion Device [Internet]. Available from: http://www.accessdata.fda.gov/cdrh_docs/pdf/P000058b.pdf. Accessed: Feb 14, 2010.
  71. Carragee EJ, Chu G, Rohatgi R, et al. Cancer risk after use of recombinant bone morphogenetic protein-2 for spinal arthrodesis. J Bone Joint Surg Am. 2013;95(17):1537–1545. doi: 10.2106/jbjs.l.01483
  72. Kelly MP, Savage JW, Bentzen SM, et al. Cancer risk from bone morphogenetic protein exposure in spinal arthrodesis. J Bone Joint Surg Am. 2014;96(17):1417–1422. doi: 10.2106/jbjs.m.01190
  73. Wang X, Huang J, Huang F, et al. Bone morphogenetic protein 9 stimulates callus formation in osteoporotic rats during fracture healing. Mol Med Rep. 2017;15(5):2537–2545. doi: 10.3892/mmr.2017.6302
  74. Rittenberg B, Partridge E, Baker G, et al. Regulation of BMP-induced ectopic bone formation by Ahsg. J Orthop Res. 2005;23(3):653–662. doi: 10.1016/j.orthres.2004.11.010
  75. Ueland T, Stilgren L, Bollerslev J. Bone matrix levels of dickkopf and sclerostin are positively correlated with bone mass and strength in postmenopausal osteoporosis. Int J Mol Sci. 2019;20(12):2896. doi: 10.3390/ijms20122896

补充文件

附件文件
动作
1. JATS XML
下载
2. Fig. 1. The mechanism of action of bone morphogenetic proteins during bone tissue regeneration. Proteins recruit and induce the proliferation of mesenchymal stem cells, which differentiate into chondrocytes and osteoblasts. "+" - stimulating effect; TGF-β - transforming growth factor beta; IL-1 - interleukin-1; IL-6 - interleukin-6; PDGF - platelet growth factor; FGF - fibroblast growth factor

下载 (402KB)
索引源数据
3. Fig. 2. Signal transmission scheme of bone morphogenetic proteins for induction of osteogenic differentiation of mesenchymal stem cells. ALP - alkaline phosphatase; OSN - osteocalcin; Id1 - inhibitor of DNA binding 1; ERK - kinase regulated by extracellular signals; SMAD - signal converters and transcription modulators

下载 (456KB)
索引源数据

版权所有 © Mukhametov U., Lyulin S., Borzunov D., Gareev I., 2021

Creative Commons License
此作品已接受知识共享署名 4.0国际许可协议的许可
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 71733 от 08.12.2017.


##common.cookie##