Skip to main content

Advertisement

Log in

Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts

  • Original Article
  • Published:
Journal of Bone and Mineral Metabolism Aims and scope Submit manuscript

Abstract

In the present study, the effects of bone morphogenetic protein-2 (BMP-2), vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) on regulation of rat osteoblast (ROB) maturation in vitro were investigated. It was found that the proliferation, differentiation and mineralization of ROBs were all dose-dependently increased at particular times in the case of treatment with only one growth factor. To investigate the effects of combined treatment, ROBs were treated with either a single application of a relatively high dose of each growth factor, or binary/triple combined applications of relatively low doses of the growth factors. Osteogenic differentiation was significantly promoted in the triple combination treatment of BMP-2, VEGF and bFGF compared with the single or binary combination treatments. The optimal timing of the triple combination to enhance osteogenesis was also tested. When bFGF and VEGF were added in the early stage, and BMP-2 and VEGF were added in the late stage, osteogenic differentiation of ROBs could be enhanced more effectively. These results could be used to construct bone tissue engineering scaffolds that release growth factors sequentially.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Zhao Z, Zhao M, Xiao G, Franceschi RT (2005) Gene transfer of the Runx2 transcription factor enhances osteogenic activity of bone marrow stromal cells in vitro and in vivo. Mol Ther 12:247–253

    Article  CAS  PubMed  Google Scholar 

  2. Fu Y-C, Nie H, Ho M-L, Wang C-K, Wang C-H (2008) Optimized bone regeneration based on sustained release from three-dimensional fibrous PLGA/HAp composite scaffolds loaded with BMP-2. Biotechnol Bioeng 99:996–1006

    Article  CAS  PubMed  Google Scholar 

  3. Nie H, Soh BW, Fu Y-C, Wang C-H (2008) Three-dimensional fibrous PLGA/HAp composite scaffold for BMP-2 delivery. Biotechnol Bioeng 99:223–234

    Article  CAS  PubMed  Google Scholar 

  4. Kempen DHR, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJA (2009) Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials 30:2816–2825

    Article  CAS  PubMed  Google Scholar 

  5. Deckers MM, Karperien M, van der Bent C, Yamashita T, Papapoulos SE, Löwik CW (2000) Expression of vascular endothelial growth factors and their receptors during osteoblast differentiation. Endocrinology 141:1667–1674

    Article  CAS  PubMed  Google Scholar 

  6. Grasselli F, Basini G, Bussolati S, Tamanini C (2002) Effects of VEGF and bFGF on proliferation and production of steroids and nitric oxide in porcine granulosa cells. Reprod Domest Anim 37:362–368

    Article  CAS  PubMed  Google Scholar 

  7. Tsutsumi S, Shimazu A, Miyazaki K, Pan H, Koike C, Yoshida E, Takagishi K, Kato Y (2001) Retention of multilineage differentiation potential of mesenchymal cells during proliferation in response to FGF. Biochem Biophys Res Commun 288:413–419

    Article  CAS  PubMed  Google Scholar 

  8. Fujimura K, Bessho K, Okubo Y, Kusumoto K, Segami N, Lizuka T (2002) The effect of fibroblast growth factor-2 on the osteoinductive activity of recombinant human bone morphogenetic protein-2 in rat muscle. Arch Oral Biol 47:577–584

    Article  CAS  PubMed  Google Scholar 

  9. Chaudhary LR, Hofmeister AM, Hruska KA (2004) Differential growth factor control of bone formation through osteoprogenitor differentiation. Bone 34:402–411

    Article  CAS  PubMed  Google Scholar 

  10. Nishimori S, Tanaka Y, Chiba T, Fujii M, Imamura T, Miyazono K, Ogasawara T, Kawaguchi H, Igarashi T, Fujita T, Tanaka K, Toyoshima H (2001) Smad-mediated transcription is required for transforming growth factor-β1-induced p57Kip2 proteolysis in osteoblastic cells. J Biol Chem 276:10700–10705

    Article  CAS  PubMed  Google Scholar 

  11. Song I, Kim B-S, Kim C-S, Im G-I (2011) Effects of BMP-2 and vitamin D3 on the osteogenic differentiation of adipose stem cells. Biochem Biophys Res Co 408:126–131

    Article  CAS  Google Scholar 

  12. Camozzi V, Tossi A, Simoni E, Pagani F, Francucci CM, Moro L (2007) Role of biochemical markers of bone remodeling in clinical practice. J Endocrinol Invest 30:13–17

    Article  CAS  PubMed  Google Scholar 

  13. Blanco Calvo M, Bolós Fernández V, Medina Villaamil V, Aparicio Gallego G, Díaz Prado S, Grande Pulido E (2009) Biology of BMP signaling and cancer. Clin Transl Oncol 11:126–137

    Article  CAS  PubMed  Google Scholar 

  14. Miyazono K, Maeda S, Imamura T (2005) BMP receptor signaling: transcriptional targets regulation of signals, and signaling cross-talk. Cytokine Growth Factor Rev 16:251–263

    Article  CAS  PubMed  Google Scholar 

  15. Ryoo HM, Lee MH, Kim YJ (2006) Critical molecular switches involved in BMP-2-induced osteogenic differentiation of mesenchymal cells. Gene 366:51–57

    Article  CAS  PubMed  Google Scholar 

  16. Peng H, Usas A, Olshanski A, Ho AM, Gearhart B, Cooper GM, Huard J (2005) VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis. J Bone Miner Res 20:2017–2027

    Article  CAS  PubMed  Google Scholar 

  17. Celil AB, Campbell PG (2005) BMP-2 and insulin-like growth factor-I mediate Osterix (Osx) expression in human mesenchymal stem cells via the MAPK and protein kinase D signaling pathways. J Biol Chem 280:31353–31359

    Article  CAS  PubMed  Google Scholar 

  18. Deschaseaux F, Sensébée L, Heymann D (2009) Mechanisms of bone repair and regeneration. Trends Mol Med 15:417–429

    Article  CAS  PubMed  Google Scholar 

  19. Maegawa N, Kawamura K, Hirose M, Yajima H, Takakura Y, Ohgushi H (2007) Enhancement of osteoblastic differentiation of mesenchymal stromal cells cultured by selective combination of bone morphogenetic protein-2 (BMP-2) and fibroblast growth factor-2 (FGF-2). J Tissue Eng Regen Med 1:306–313

    Article  CAS  PubMed  Google Scholar 

  20. Fakhry A, Ratisoontorn C, Vedhachalam C, Salhab I, Koyama E, Leboy P, Pacifici M, Kirschner RE, Nah H-D (2005) Effects of FGF-2/-9 in calvarial bone cell cultures: differentiation stage-dependent mitogenic effect, inverse regulation of BMP-2 and noggin, and enhancement of osteogenic potential. Bone 36:254–266

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work has been supported by the Subjects of National Natural Science Foundation of China (51173120, 51273122, and 51202151).

Conflict of interest

All authors state that they have no conflicts of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Guangfu Yin.

About this article

Cite this article

Li, P., Bai, Y., Yin, G. et al. Synergistic and sequential effects of BMP-2, bFGF and VEGF on osteogenic differentiation of rat osteoblasts. J Bone Miner Metab 32, 627–635 (2014). https://doi.org/10.1007/s00774-013-0538-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00774-013-0538-6

Keywords

Navigation