Skip to main content
SpringerLink
Log in

Recombinant Human Bone Growth Factor BMP-2 Produced in Escherichia coli. Part 1: From Protein Purification to Experimental Models for Efficacy Research

  • REVIEWS
  • Published:
Molecular Genetics, Microbiology and Virology Aims and scope Submit manuscript

Abstract

Here, we give an overview of purification of the recombinant BMP-2 produced in Escherichia coli and its efficacy in bone tissue regeneration as a constituent of different osteoplastic materials. Protein production in this heterologous system and its subsequent purification and refolding resulting in the active protein are described. The efficacy of BMP-2 originated from prokaryotic cells in osteogenesis induction, which is similar to the efficacy of that produced in eukaryotic cells, has been demonstrated in many studies with the variety of carriers and animal models. In this review, the databases PubMed Central (United States National Institutes of Health’s National Library of Medicine, NIH/NLM), PubMed (NLM National Center for Biotechnology Information, NCBI), and e-library (Scientific Electronic Library) were used.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1.

Similar content being viewed by others

REFERENCES

  1. Wozney, J.M., Rosen, V., Celeste, A.J., Mitsock, L.M., Whitters, M.J., Kriz, R.W., et al., Novel regulators of bone formation: Molecular clones and activities, Science, 1988, vol. 242, pp. 1528–1534. https://doi.org/10.1126/science.3201241

    Article  CAS  PubMed  Google Scholar 

  2. Israel, D.I., Nove, J., Kerns, K.M., Moutsatsos, I.K., and Kaufman, R.J., Expression and characterization of bone morphogenetic protein-2 Chinese hamster ovary cells, Growth Factors, 1992, vol. 7, no. 2, pp. 139–150.

    Article  CAS  Google Scholar 

  3. Scheuxer, C., Sebald, W., and Hulsmeyer, M., Crystal structure of human bone morphogenetic protein-2 at 2.7 Å resolution, J. Mol. Biol., 1999, vol. 287, no. 1, pp. 103–115. https://doi.org/10.1006/jmbi.1999.2590

    Article  Google Scholar 

  4. Granjeiro, J.M., Bone morphogenetic proteins: From structure to clinical use, Braz. J. Med. Biol. Res., 2005, vol. 38, no. 10, pp. 1463–1473. https://doi.org/10.1590/s0100-879x2005001000003

    Article  CAS  PubMed  Google Scholar 

  5. Zaitsev, V.V., Karyagina, A.S., and Lunin, V.G., Bone morphogenetic proteins (BMP): General characteristics, prospects for clinical application in traumatology and orthopedics, Vestn. Travmatol. Ortop. im. N.N. Priorova, 2009, no. 4, pp. 79–84.

  6. Li, R.H. and Wozney, J.M., Delivering on the promise of bone morphogenetic proteins, Trends Biotechnol., 2001, vol. 19, no. 7, pp. 255–265.

    Article  CAS  Google Scholar 

  7. Kirker-Head, C.A., Potential applications and delivery strategies for bone morphogenetic proteins, Adv. Drug Delivery Rev., 2000, vol. 43, no. 1, pp. 65–92.

    Article  CAS  Google Scholar 

  8. Kim, I.S., Lee, E.N., Cho, T.H., Song, Y.M., Hwang, S.J., Oh, J.H., et al., Promising efficacy of Escherichia coli recombinant human bone morphogenetic protein-2 in collagen sponge for ectopic and orthotopic bone formation and comparison with mammalian cell recombinant human bone morphogenetic protein-2, Tissue Eng., Part A, 2011, vol. 17, nos. 3–4, pp. 337–348. https://doi.org/10.1089/ten.TEA.2010.0408

    Article  Google Scholar 

  9. Jin, Y.Z., Zheng, G.B., and Lee, J.H., Escherichia coli BMP-2 showed comparable osteoinductivity with Chinese hamster ovary derived BMP-2 with demineralized bone matrix as carrier, Growth Factors, 2019, vol. 4, pp. 1–10. https://doi.org/10.1080/08977194.2019.1596905

    Article  CAS  Google Scholar 

  10. Gintsburg, A.L., Karyagina, A.S., Lunin, V.G., and Semikhin, A.S., Development of new generation drugs for effective bone tissue regeneration, Lech. Profil., 2011, vol. 1, no. 1, pp. 80–84.

    Google Scholar 

  11. Gintsburg, A.L., Sharapova, N.E., Nadezhdin, S.V., Fedorova, M.Z., Karyagina, A.S., and Lunin, V.G., New drugs for stimulating bone tissue regeneration, Sovrem. Med. Tekhnol., 2011, vol. 7, pp. 60–62.

    Google Scholar 

  12. Donchenko, S.V., Karyagina, A.S., Alekseev, D.V., and Lunin, V.G., First experience for applying new generation osteoplastic materials containing recombinant human bone morphogenetic proteins (rhBMPs) for defects and post-traumatic bone tissue pathology, Mosk. Med. Zh., 2012, vol. 4, pp. 16–21.

    Google Scholar 

  13. Bartov, M.S., Karyagina, A.S., Gromov, A.V., Mishina, D.M., Trunova, G.V., Sidorova, E.I., et al., New generation osteoplastic drugs “Gamalant” containing factors for growth and bone tissue regeneration, Kafedra Travmatol. Ortop., 2012, vol. 2, pp. 21–25.

    Google Scholar 

  14. Olesova, V.N., Kononenko, V.I., Bersanov, R.U., Kashchenko, P.V., Nikonchuk, E.E., and Chuyanova, E.Yu., Pre-implantation preparation of an alveolar hole of an extracted tooth using domestic material Gamalant™ paste-FORTE Plus, Farmateka, 2013, vol. 2, pp. 28–30.

    Google Scholar 

  15. Huh, J.-B., Lee, H.-J., Jang, J.-W., Kim, M.-J., Yun, P.-Y., Kim, S.-H., et al., Randomized clinical trial on the efficacy of Escherichia coli-derived rhBMP-2 with β-TCP/HA in extraction socket, J. Adv. Prosthodontics, 2011, vol. 3, no. 3, pp. 161–165. https://doi.org/10.4047/jap.2011.3.3.161

    Article  Google Scholar 

  16. Ruppert, R., Hoffmann, E., and Sebald, W., Human bone morphogenetic protein 2 contains a heparin-binding site which modifies its biological activity, Eur. J. Biochem., 1996, vol. 237, no. 1, pp. 295–302.

    Article  CAS  Google Scholar 

  17. Vallejo, L.F., Brokelmann, M., Marten, S., Trappe, S., Cabrera-Crespo, J., Hoffmann, A., et al., Renaturation and purification of bone morphogenetic protein-2 produced as inclusion bodies in high-cell-density cultures of recombinant Escherichia coli, J. Biotechnol., 2002, vol. 94, no. 2, pp. 185–194.

    Article  CAS  Google Scholar 

  18. Vallejo, L.F. and Rinas, U., Optimized procedure for renaturation of recombinant human bone morphogenetic protein-2 at high protein concentration, Biotechnol. Bioeng., 2004, vol. 85, no. 6, pp. 601–609. https://doi.org/10.1002/bit.10906

    Article  CAS  PubMed  Google Scholar 

  19. Boix, T., Gomez-Morales, J., Torrent-Burgues, J., Monfort, A., Puigdomenech, P., and Rodriguez-Clemente, R., Adsorption of recombinant human bone morphogenetic protein rhBMP-2 onto hydroxyapatite, J. Inorg. Biochem., 2005, vol. 99, no. 5, pp. 1043–1050. https://doi.org/10.1016/j.jinorgbio.2005.01.011

    Article  CAS  PubMed  Google Scholar 

  20. Long, S., Truong, L., Bennett, K., Phillips, A., Wong-Staal, F., and Ma, H., Expression, purification and renaturation of bone morphogenetic protein-2 from Escherichia coli, Protein Expression Purif., 2006, vol. 46, no. 2, pp. 374–378. https://doi.org/10.1016/j.pep.2005.09.025

    Article  CAS  Google Scholar 

  21. Zhang, H., Wu, J., Zhang, Y., Fu, N., Wang, J., and Zhao, S., Optimized procedure for expression and renaturation of recombinant human bone morphogenetic protein-2 at high protein concentrations, Mol. Biol., 2010, vol. 37, no. 7, pp. 3089–3095. https://doi.org/10.1002/bit.10906

    Article  CAS  Google Scholar 

  22. Von Einem, S., Schwarz, E., and Rudolph, R., A novel two-step renaturation procedure for efficient production of recombinant BMP-2, Protein Expression Purif., 2010, vol. 73, no. 1, pp. 65–69. https://doi.org/10.1016/j.pep.2010.03.009

    Article  CAS  Google Scholar 

  23. Nasrabadi, D., Rezaeiani, S., Sayadmanesh, A., Eslaminejad, M.B., and Shabani, A., Inclusion body expression and refolding of recombinant bone morphogenetic protein-2, Avicenna J. Med. Biotechnol., 2018, vol. 10, no. 4, pp. 202–207.

    PubMed  PubMed Central  Google Scholar 

  24. Zhang, Y., Ma, Y., Yang, M., Min, S., Yao, J., and Zhu, L., Expression, purification, and refolding of a recombinant human bone morphogenetic protein 2 in vitro, Protein Expression Purif., 2011, vol. 75, no. 2, pp. 155–160. https://doi.org/10.1016/j.pep.2010.07.014

    Article  CAS  Google Scholar 

  25. Sharapova, N.E., Kotnova, A.P., Galushkina, Z.M., Lavrova, N.V., Poletaeva, N.N., Tukhvatulin, A.E., et al., Production of the recombinant human bone morphogenetic protein-2 in Escherichia coli and testing of its biological activity in vitro and in vivo, Mol. Biol. (Moscow), 2010, vol. 44, no. 6, pp. 923–930.

    Article  CAS  Google Scholar 

  26. Karyagina, A.S., Boksha, I.S., Grunina, T.M., Demidenko, A.V., Poponova, M.S., Sergienko, O.V., et al., Optimization of rhBMP-2 active-form production in a heterologous expression system using microbiological and molecular genetic approaches, Mol. Genet., Microbiol. Virol., 2016, vol. 31, no. 4, pp. 208–213. https://doi.org/10.3103/S0891416816040030

    Article  Google Scholar 

  27. Karyagina, A.S., Boksha, I.S., Grunina, T.M., Demidenko, A.V., Poponova, M.S., Sergienko, O.V., et al., Two variants of recombinant human bone morphogenetic protein 2 (rhBMP-2) with additional protein domains: synthesis in an Escherichia coli heterologous expression system, Biochemistry (Moscow), 2017, vol. 82, no. 5, pp. 613–624. https://doi.org/10.1134/S0006297917050091

    Article  CAS  PubMed  Google Scholar 

  28. Ihm, H.J., Yang, S.J., Huh, J.W., Choi, S.Y., and Cho, S.W., Soluble expression and purification of synthetic human bone morphogenetic protein-2 in Escherichia coli, BMB Rep., 2008, vol. 41, no. 5, pp. 404–407. https://doi.org/10.5483/BMBRep.2008.41.5.404

    Article  CAS  PubMed  Google Scholar 

  29. Retnoningrum, D.S., Pramesti, H.T., Santika, P.Y., Valerius, O., Asjarie, S., and Suciati, T., Codon optimization for high level expression of human bone morphogenetic protein-2 in Escherichia coli, Protein Expression Purif., 2012, vol. 84, no. 2, pp. 188–194. https://doi.org/10.1016/j.pep.2012.05.010

    Article  CAS  Google Scholar 

  30. Rane, A.M., Jonnalagadda, S., and Li, Z., On-column refolding of bone morphogenetic protein-2 using cation exchange resin, Protein Expression Purif., 2013, vol. 90, no. 2, pp. 135–140. https://doi.org/10.1016/j.pep.2013.05.008

    Article  CAS  Google Scholar 

  31. Bartov, M.S., Gromov, A.V., Poponova, M.S., Savina, D.M., Nikitin, K.E., Grunina, T.M., et al., Modern approaches to research of new osteogenic biomaterials on the model of regeneration of cranial critical-sized defects in rats, Bull. Exp. Biol. Med., 2016, vol. 162, no. 2, pp. 273–276. https://doi.org/10.1007/s10517-016-3593-x

    Article  CAS  PubMed  Google Scholar 

  32. Bartov, M.S., Gromov, A.V., Manskih, V.N., Makarova, E.B., Rubshtein, A.P., Poponova, M.S., et al., Recombinant human bone morphogenetic protein-2 (rhBMP-2) with additional protein domain synthesized in E. coli: In vivo osteoinductivity in experimental models on small and large laboratory animals, Bull. Exp. Biol. Med., 2017, vol. 164, no. 2, pp. 148–151. https://doi.org/10.1007/s10517-017-3945-1

    Article  CAS  PubMed  Google Scholar 

  33. Gaifullin, N.M., Karyagina, A.S., Gromov, A.V., Terpilovskii, A.A., Malanin, D.A., Demeshchenko, M.V., et al., Morphological characteristics of osseointegration after-application of titanium implants with bioactive coating and recombinant bone morphogenetic protein rhBMP-2, Morfologiya, 2016, vol. 149, no. 1, pp. 77–84.

    CAS  Google Scholar 

  34. Andreev, A.Yu., Zakharov, V.D., Zairat’yants, O.V., Borzenok, S.A., Khubetsova, M.Kh., Osidak, E.O., et al., Prospects for using bone growth factor as a component of collagen matrix for cornea strengthening (experimental study), Sovrem. Tekhnol. Oftal’mol., 2016, vol. 4, pp. 11–16.

    Google Scholar 

  35. Zakharov, V.D., Andreev, A.Yu., Zairat’yants, O.V., Osidak, E.O., Borzenok, S.A., Krasheninnikov, S.V., et al., Morphological changes in rabbit cornea caused by the bone and cartilage rhBMP-2 growth factor as a component of intracorneal collagen implant, Klin. Eksp. Morfol., 2016, vol. 4, pp. 36–42.

    Google Scholar 

  36. Zakharov, V.D., Zairat’yants, O.V., Andreev, A.Yu., Osidak, E.O., Borzenok, S.A., and Krasheninnikov, S.V., et al., Influence of rhBMP-2 growth factor in composition with collagen carrier on morphological and biomechanical characteristics of cornea, Fedorov J. Ophthalmic Surg., 2016, no. 4, pp. 20–28.

  37. Pramesti, H.T., Suciati, T., Indrayati, A., Asjarie, S., and Retnoningrum, D.S., Recombinant human Bone Morphogenetic Protein-2: Optimization of overproduction, solubilization, renaturation and its characterization, Biotechnology, 2012, vol. 11, no. 3, pp. 133–143. https://doi.org/10.3923/biotech.2012.133.143

    Article  CAS  Google Scholar 

  38. Chen, B., Lin, H., Zhao, Y., Wang, B., Zhao, Y., Liu, Y., et al., Activation of demineralized bone matrix by genetically engineered human bone morphogenetic protein-2 with a collagen binding domain derived from von Willebrand factor propolypeptide, J. Biomed. Mater. Res., Part A, 2007, vol. 80, no. 2, pp. 428–434. https://doi.org/10.1002/jbm.a.30900

    Article  CAS  Google Scholar 

  39. Han, X., Zhang, W., Gu, J., Zhao, H., Ni, L., Han, J., et al., Accelerated postero-lateral spinal fusion by collagen scaffolds modified with engineered collagen-binding human bone morphogenetic protein-2 in rats, PLoS One, 2014, vol. 9, no. 5, p. e98 480. https://doi.org/10.1371/journal.pone.0098480

    Article  CAS  Google Scholar 

  40. Cahill, K.S., Chi, J.H., Day, A., and Claus, E.B., Prevalence, complications, and hospital charges associated with use of bone-morphogenetic proteins in spinal fusion procedures, JAMA,J. Am. Med. Assoc., 2009, vol. 302, no. 1, pp. 58–66. https://doi.org/10.1001/jama.2009.956

    Article  CAS  Google Scholar 

  41. Carragee, E.J., Hurwitz, E.L., and Weiner, B.K., A critical review of recombinant human bone morphogenetic protein-2 trials in spinal surgery: Emerging safety concerns and lessons learned, Spine J., 2011, vol. 11, no. 6, pp. 471–491. https://doi.org/10.1016/j.spinee.2011.04.023

    Article  PubMed  Google Scholar 

  42. Gamradt, S.C. and Lieberman, J.R., Genetic modification of stem cells to enhance bone repair, Ann. Biomed. Eng., 2004, vol. 32, no. 1, pp. 136–147. https://doi.org/10.1023/B:ABME.0000007798.78548.b8

    Article  PubMed  Google Scholar 

  43. Yang, H.S., La, W.-G., Cho, Y.-M., Shin, W., Yeo, G.-D., and Kim, B.-S., Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration, Exp. Mol. Med., 2012, vol. 44, no. 5, pp. 350–355. https://doi.org/10.3858/emm.2012.44.5.039

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Nam, J.-W. and Kim, H.-J., Stepwise verification of bone regeneration using recombinant human bone morphogenetic protein-2 in rat fibula model, J. Korean Assoc. Oral Maxillofac. Surg., 2017, vol. 43, no. 6, pp. 373–387. https://doi.org/10.5125/jkaoms.2017.43.6.373

    Article  PubMed  PubMed Central  Google Scholar 

  45. Guzman, R., Nardecchia, S., Gutierrez, M.C., Ferrer, M.L., Ramos, V., del Monte, F., et al., Chitosan scaffolds containing calcium phosphate salts and rhBMP-2: in vitro and in vivo testing for bone tissue regeneration, PLoS One, 2014, vol. 9, no. 2, p. e87 149. https://doi.org/10.1371/journal.pone.0087149

    Article  CAS  Google Scholar 

  46. Abarrategi, A., Moreno-Vicente, C., Martınez-Vazquez, F.J., Civantos, A., Ramos, V., Sanz-Casado, J.V., et al., Biological properties of solid free form designed ceramic scaffolds with BMP-2: In vitro and in vivo evaluation, PLoS One, 2012, vol. 7, no. 3, p. e34 117. https://doi.org/10.1371/journal.pone.0034117

    Article  CAS  Google Scholar 

  47. Huang, B., Yuan, Y., Li, T., Ding, S., Zhang, W., Gu, Y., et al., Facilitated receptor-recognition and enhanced bioactivity of bone morphogenetic protein-2 on magnesium-substituted hydroxyapatite surface, Sci. Rep., 2016, vol. 6, p. 24 323. https://doi.org/10.1038/srep24323

    Article  CAS  Google Scholar 

  48. Dohzono, S., Imai, Y., Nakamura, H., Wakitani, S., and Takaoka, K., Successful spinal fusion by E. coli-derived BMP-2-adsorbed porous β-TCP granules6 a pilot study, Clin. Orthop. Relat. Res., 2009, vol. 476, no. 12, pp. 3206–3212. https://doi.org/10.1007/s11999-009-0960-1

    Article  Google Scholar 

  49. Patel, J., Flanagan, C.L., and Hollister, S.J., Bone morphogenetic protein-2 adsorption onto poly-ε-caprolactone better preserves bioactivity in vitro and produces more bone in vivo than conjugation under clinically relevant loading scenarios, Tissue Eng., 2015, vol. 21, no. 5, pp. 489–498. https://doi.org/10.1089/ten.TEC.2014.0377

    Article  CAS  Google Scholar 

  50. Moser, N., Lohse, N., Goldstein, J., Kauffmann, P., Sven, B., Epple, M., et al., Do we need retarded delivery of bone growth factors in facial bone repaire? An experimental study in rats, Eur. Cells Mater., 2017, vol. 134, pp. 162–179. https://doi.org/10.22203/eCM.v034a11

    Article  Google Scholar 

  51. Sharma, A., Meyer, F., Hyvonen, M., Best, S.M., Cameron, R.E., and Rushton, N., Osteoinduction by combining bone morphogenetic protein (BMP)-2 with a bioactive novel nanocomposite, Bone Jt. Res., 2012, vol. 1, no. 7, pp. 145–151. https://doi.org/10.1302/2046-3758.17.2000082

    Article  CAS  Google Scholar 

  52. Charles, L.F., Woodman, J.L., Ueno, D., Gronowicz, G., Hurley, M.M., and Kuhn, L.T., Effects of low dose FGF-2 and BMP-2 on healing of calvarial defects in old mice, Exp. Gerontol., 2015, vol. 64, pp. 62–69. https://doi.org/10.1016/j.exger.2015.02.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Kim, S.-G., Jeong, J.-H., Che, X., Park, Y.-T., Lee, S.-W., Jung, E.-S., et al., Reconstruction of radial bone defect using gelatin sponge and a BMP-2 combination graft, BMB Rep., 2013, vol. 46, no. 6, pp. 328–333. https://doi.org/10.5483/BMBRep.2013.46.6.231

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Hauff, K., Zambarda, C., Dietrich, M., Halbig, M., Grab, A.L., Medda, R., et al., Matrix-immobilized BMP-2 on microcontact printed fibronectin as an in vitro tool to study BMP-mediated signaling and cell migration, Front. Bioeng. Biotechnol., 2015, vol. 3, p. 62. https://doi.org/10.3389/fbioe.2015.00062

    Article  PubMed  PubMed Central  Google Scholar 

  55. Huh, J.-B., Yang, J.-J., Choi, K.-H., Bae, J.H., Lee, J.-Y., Kim, S.-E., et al., Effect of rhBMP-2 immobilized anorganic bovine bone matrix on bone regeneration, Int. J. Mol. Sci., 2015, vol. 16, no. 7, pp. 16 034–16 052. https://doi.org/10.3390/ijms160716034

    Article  CAS  Google Scholar 

  56. Kim, S.-Y., Lee, Y., Seo, S.-J., Lim, J.-H., and Kim, Y.-G., Effects of Escherichia coli-derived recombinant human bone morphogenetic protein-2 loaded porous hydroxyaptite-based ceramics on calvarial defect in rabbits, J. Bone Metab., 2017, vol. 24, no. 1, pp. 23–30. https://doi.org/10.11005/jbm.2017.24.1.23

    Article  PubMed  PubMed Central  Google Scholar 

  57. Kuroiwa, Y., Niikura, T., Lee, S.Y., Oe, K., Iwakura, T., Fukui, T., Matsumoto, T., et al., Escherichia coli-derived BMP-2-absorbed β-TCP granules induce bone regeneration in rabbit critical-sized femoral segmental defects, Int. Orthop., 2019, vol. 43, no. 5, pp. 1247–1253. https://doi.org/10.1007/s00264-018-4079-4

    Article  PubMed  Google Scholar 

  58. Peeters, M., Detiger, S.E.L., Karfeld-Sulzer, L.S., Smit, T.H., Yayon, A., Weber, F.E., et al., BMP-2 and BMP-2/7 heterodimers conjugated to a fibrin/hyaluronic acid hydrogel in a large animal model of mild intervertebral disc degeneration, BioRes. Open Access., 2015, vol. 4, no. 1, pp. 398–406. https://doi.org/10.1089/biores.2015.0025

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Schmitz, J.P. and Hollinger, J.O., The critical size defect as an experimental model for craniomandibulofacial nonunions, Clin. Orthop. Relat. Res., 1986, vol. 205, pp. 299–308.

  60. Szpalski, C., Barr, J., Wetterau, M., Saadeh, P.B., and Warren, S.M., Cranial bone defects: Current and future strategies, Neurosurg. Focus, 2010, vol. 29, no. 6, p. E8. https://doi.org/10.3171/2010.9.FOCUS10201

    Article  PubMed  Google Scholar 

  61. Lee, J.H., Kim, C.S., Choi, K.H., Jung, U.W., Yun, J.H., Choi, S.H., et al., The induction of bone formation in rat calvarial defects and subcutaneous tissues by recombinant human BMP-2, produced in Escherichia coli, Biomaterials, 2010, vol. 31, no. 13, pp. 3512–3519. https://doi.org/10.1016/j.biomaterials.2010.01.075

    Article  CAS  PubMed  Google Scholar 

  62. Horner, E.A., Kirkham, J., Wood, D., Curran, S., Smith, M., Thomson, B., et al., Long bone defect models for tissue engineering applications: Criteria for choice, Tissue Eng.,Part B, 2010, vol. 16, no. 2, pp. 263–271. https://doi.org/10.1089/ten.TEB.2009.0224

    Article  Google Scholar 

  63. Matsumoto, T., Toyoda, H., Dohzono, S., Yasuda, H., Wakitani, S., Nakamura, H., et al., Efficacy of interspinous process lumbar fusion with recombinant human bone morphogenetic protein-2 delivered with a synthetic polymer and β-tricalcium phosphate in a rabbit model, Eur. Spine J., 2012, vol. 21, no. 7, pp. 1338–1345. https://doi.org/10.1007/s00586-011-2130-x

    Article  PubMed  Google Scholar 

  64. Lee, J.-S., Kim, T.-W., Park, S., Kim, B.-S., Im, G.-I., Cho, K.-S., et al., Reduction of adipose tissue formation by the controlled release of BMP-2 using a hydroxyapatite-coated collagen carrier system for sinus-augmentation/extraction-socket grafting, Materials (Basel), 2015, vol. 8, no. 11, pp. 7634–7649. https://doi.org/10.3390/ma8115411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Yuasa, M., Yamada, T., Taniyama, T., Masaoka, T., Xuetao, W., Yoshii, T., et al., Dexamethasone enhances osteogenic differentiation of bone marrow- and muscle-derived stromal cells and augments ectopic bone formation induced by bone morphogenetic protein-2, PLoS One, 2015, vol. 10, no. 2, p. e0 116 462. https://doi.org/10.1371/journal.pone.0116462

    Article  CAS  Google Scholar 

Download references

ACKNOWLEDGMENTS

The authors thank I. Bokshe for useful discussion.

Funding

This study was supported by the Russian Scientific Foundation, grant no. 16-15-00133.

Author information

Authors and Affiliations

  1. Gamaleya National Research Center of Epidemiology and Microbiology, Ministry of Healthcare of the Russian Federation, 123098, Moscow, Russia

    A. V. Gromov, M. S. Poponova & A. S. Karyagina

  2. All Russia Research Institute of Agricultural Biotechnology, 127550, Moscow, Russia

    A. S. Karyagina

  3. Belozersky Institute of Physicochemical Biology, Moscow State University, 119234, Moscow, Russia

    A. S. Karyagina

Authors
  1. A. V. Gromov
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. S. Poponova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. A. S. Karyagina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to A. V. Gromov, M. S. Poponova or A. S. Karyagina.

Ethics declarations

COMPLIANCE WITH ETHICAL STANDARDS

The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

ADDITIONAL INFORMATION

To cite this article: A.V. Gromov, M.S. Poponova, and A.S. Karyagina. “Recombinant Human Bone Growth Factor BMP-2 Produced in Escherichia coli. Part 1: From Protein Purification to Experimental Models for Efficacy Research.” Molekulyarnaya Genetika, Mikrobiologiya i Virusologya (Russian Molecular Genetics, Microbiology, and Virology), 2020, vol. 38, no. 1, pp. 24–34. https://doi.org/10.17116/molgen20203801124

Additional information

Translated by A. Boutanaev

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Gromov, A.V., Poponova, M.S. & Karyagina, A.S. Recombinant Human Bone Growth Factor BMP-2 Produced in Escherichia coli. Part 1: From Protein Purification to Experimental Models for Efficacy Research. Mol. Genet. Microbiol. Virol. 35, 22–31 (2020). https://doi.org/10.3103/S0891416820010036

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.3103/S0891416820010036

Keywords:

Search

Navigation