Recombinant human BMP-2/-7 heterodimer protein expression for bone tissue engineering using recombinant baculovirus expression system

  • Park, Seung-Won ;
  • Goo, Tae-Won ;
  • Kim, Seong Ryul ;
  • Choi, Kwang-Ho
  • Received : 2016.04.04
  • Accepted : 2016.06.20
  • Published : 2016.06.30


Bone morphogenetic proteins (BMPs) are essential growth factors for bone formation, skeletal development and bone regeneration. The BMP-2/7 heterodimer is known to have remarkable effects on osteogenic induction that are even stronger than the BMP-2 or BMP-7 homodimers. We designed a recombinant human BMP-2/7 (rhBMP-2/7) heterodimer protein with four glycine residues between BMP-2 and BMP-7 protein to facilitate free bond rotation of domains. The Baculovirus Expression Vector System (BEVS) is routinely used to produce recombinant proteins in the milligram scale. In this study, the BEVS was used to express the rhBMP-2/7 protein whrer the recombinant baculovirus was recovered in the host Sf9 cells. To confirm the biological activity of rhBMP-2/7 protein secreted from the BEVS as an osteogenic differentiation and induction factor, we measured the BMP-induced ALP activity. rhBMP-2/7 could be used as an alternative to BMPs to overcome limitations like short half-life and requirement for high concentrations. Furthermore, rhBMP-2/7 may be an efficient tool for various application studies such as bone regeneration and skeletal development.


BEVS;rhBMP- 2/7;bone formation;tissue-engineering


  1. Hu Yu-chen. Baculovirus as a highly efficient expression vector in insect and mammalian cells. Acta Pharmacologica Sinica. 2005; 26(4): 405-416.
  2. Park SW, Lee HK, Kim TG, Yoon SK, Paik SY. Hepatocyte-Specific Gene Expression by Baculovirus Pseudotyped with Vesicular Stomatitis Virus Envelope Glycoprotein. Biochem. Biophys. Res. Commun. 2001; 289: 444-450.
  3. Park SW, Choi JH, Goo TW, Kim SR, Lee GG, Kang SW. Mouse Dual Ig Domain Containing Cell Adhesion Molecule Protein Expression and Purification Using the Baculovirus Expression Vector System. J. Bacteriol. Virol. 2010; 40: 123-130.
  4. Kari J Airenne, Yu-Chen Hu, Thomas A Kost, Richard H Smith, Robert M Kotin, Chikako Ono, Yoshiharu Matsuura, Shu Wang and Seppo Ylä-Herttuala. Baculovirus: an Insect-derived Vector for Diverse Gene Transfer Applications. Molecular Therapy (2013); 21 4, 739-749.
  5. Jeong ST and Park SW. Protein Expression of the Bombyx mori Decapentaplegic Gene using the Baculovirus Expression Vector System. J Bacteriol Virol. 2015; 45: 256-261.
  6. Kataoka C, Kaname Y, Taguwa S, Abe T, Fukuhara T, Tani H, Moriishi K, Matsuura Y. Baculovirus GP64-mediated entry into mammalian cells. J Virol. 2012; 86(5): 2610-20.
  7. Makino, T., Hak, D. J., Hazelwood, S. J., Curtiss, S. and Reddi, A. H. Prevention of atrophic nonunion development by recombinant human bone morphogenetic protein-7. J. Orthop. Res. 2005; 23: 632-638.
  8. Ghosh-Choudhury. N., Harris, M. A., Feng, J. Q., Mudy G. R. and Harris S. E. Expression of the BMP2 gene during Bone cell differentiation. Crit. Rev. Euk. Gene Exp. 1994; 4: 345-355.
  9. Park SW, Kang SW, Goo TW, Kim SR, Paik SY. Extablishment of a Stable Cell Line Expressiong Human BMP2/7-PTD for Efficient Osteogenic Induction. J life Science. 2012; 22: 456-465.
  10. Ping S., Jingxiao W., Yuanna Z., Yi F. and Zhiyuan G. BMP2/7 Heterodimer is a stronger inducer of bone regeneration in peri-implant bone defects model than BMP2 or BMP7 homodimer. Dental Maerials Journal. 2012; 31(2): 239-248.
  11. Wei Zhu, Jaehon Kim, Christina Cheng, Bernard A. Rawlins, Oheneba Boachie-Adjei, Ronald G. Crystal, Chisa Hidaka. Noggin regulation of bone morphogenetic protein (BMP) 2/7 heterodimer activity in vitro. Bone. 2006; 39: 61-71.
  12. Seung-Won Park, Ji-Hyun Choi, Tae-Won Goo, Seong Ryul Kim, Gwang-Gill Lee and Seok-Woo Kang. Mouse Dual Ig Domain Containing Cell Adhesion Molecule Protein Expression and Purification Using the Baculovirus Expression Vector System. J Bacteriol Virol. 2010 Sep; 40(3): 123-130.


Grant : 재조합 거미 독 단백질 리모델링을 통한 활성 및 안전성 검증

Supported by : 대구가톨릭대학교