Skip to main content
Log in

Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits

  • Original Paper
  • Published:
International Orthopaedics Aims and scope Submit manuscript

Abstract

To assess the potential efficacy of mechano growth factor (MGF) for bone injury, we firstly investigated the effects of growth factors, including MGF, its E peptide (a short 24-amino acid C-terminal peptide, MGF-Ct24E), and insulin-like growth factor 1(IGF-1) on MC3T3-E1 osteoblast-like cell proliferation. MGF-Ct24E had the highest pro-proliferation activity among three growth factors, which was 1.4 times greater than that of IGF-1. Moreover, MGF-Ct24E promoted cell proliferation by inducing cell cycle arrest in the S and G2/M phase of the cell cycle, but also mainly by the activation of the MAPK-Erk1/2 pathway. In vivo, a 5-mm segmental bone defect in the radius of 27 rabbits was treated with MGF-Ct24E by two doses (28.5 and 57 μg /kg body weight) vs. non-growth factor injection for five consecutive days postoperatively. The cumulative rate of radiographically healed defects and histological scores of bone defect-healing revealed a statistical difference between high-dose treatment and non treatment (p < 0.01), which showed the treatment promoted defect healing. This report is the first to demonstrate that MGF-Ct24E possesses positive effects on osteoblast proliferation and bone-defect healing, suggesting a new strategy in fracture healing.

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

Similar content being viewed by others

References

  1. Skarli M, Yang SY, Bouloux P, Goldspink G (1998) Upregulation and alternative splicing of the IGF-I gene in the rabbit heart following a brief pressure/volume overload. J Physiol 9:92–193

    Google Scholar 

  2. Yang S, Alnaqeeb M, Simpson H, Goldspink G (1996) Cloning and characterization of an IGF-1 isoform expressed in skeletal muscle subjected to stretch. J Muscle Res Cell Motil 17:487–495

    Article  PubMed  CAS  Google Scholar 

  3. Hill M, Wernig A, Goldspink G (2003) Muscle satellite (stem) cell activation during local tissue injury and repair. J Anat 203:89–99

    Article  PubMed  CAS  Google Scholar 

  4. Dluzniewska J, Sarnowska A, Goldspink G, Zabłocka B (2005) A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. FASEB J 19:1896–1898

    PubMed  CAS  Google Scholar 

  5. Dimitrios M, Haralampos K, Protopapas MS, Stelios GM, Michael K (2006) Insulin-like growth factor-1 isoform mRNA expression in women with endometriosis: eutopic endometrium versus endometriotic cyst. Ann NY Acad Sci 1092:434–439

    Article  Google Scholar 

  6. Olesen JL, Heinemeier KM, Flyvbjerg A, Kjaer M (2006) Expression of insulin-like growth factor I, insulin-like growth factor binding proteins and collagen mRNA in mechanically loaded plantaris tendon. Appl Physiol 101:183–188

    Article  CAS  Google Scholar 

  7. Ates K, Yang SY, Orrell RW, Simons P (2007) The IGF-I splice variant MGF increases progenitor cells in ALS, dystrophic, and normal muscle. FEBS Lett 581:2727–2732

    Article  PubMed  CAS  Google Scholar 

  8. Mills P, Lafreniere JF, Tremblay JP (2007) A new pro-migratory activity on human myogenic precursor cells for a synthetic peptide within the E domain of the mechano growth factor. Exp Cell Res 313:5275–5237

    Article  Google Scholar 

  9. Quesada A, Micevych P, Handforth A (2009) C-terminal mechano growth factor protects dopamine neurons: A novel peptide that induces heme oxygenase-1. Exp Neurol 220:255–266

    Article  PubMed  CAS  Google Scholar 

  10. Carpenter V, Matthews K, Yang SY, Goldspink G (2008) Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction. Heart Lung Circ 17:33–39

    Article  PubMed  Google Scholar 

  11. Abbaspour A, Takata S, Matsui Y, Yasui N (2008) Continuous infusion of insulin-like growth factor-I into the epiphysis of the tibia. Int Orthop 32:395–402

    Article  PubMed  Google Scholar 

  12. Tang LL, Xian CY, Wang YL (2006) The MGF expression of osteoblasts in response to mechanical overload. Arch Oral Biol 51:1080–1085

    Article  PubMed  CAS  Google Scholar 

  13. Zhang B, Jiang P, Xian C, Tang L, Wang Y (2008) Expression of mechano-growth factor in Eschericha coli and activity analysis. Sheng Wu Gong Xue Bao 24:1180–1185 (in Chinese)

    CAS  Google Scholar 

  14. Eckardt H, Christensen KS, Lind M (2005) Recombinant human bone morphogenetic protein 2 enhances bone healing in an experimental model of fractures at risk of non-union. Injury 36:489–494

    Article  PubMed  Google Scholar 

  15. Meinel L, Zoidis E, Schneider R (2003) Localized insulin-like growth factor I delivery to enhance new bone formation. Bone 33:660–672

    Article  PubMed  CAS  Google Scholar 

  16. Yao W, Yao W, Jun Yu, Bozic T (2008) IGF-I improved bone mineral density and body composition of weaver mutant mice. Growth Horm IGF Res 18:517–525

    Article  PubMed  CAS  Google Scholar 

  17. Forriola F, Longob UG, Denaro V (2009) Platelet-rich plasma, rhOP-1® (rhBMP-7) and frozen rib allograft for the reconstruction of bony mandibular defects in sheep. A pilot experimental study. Injury Int J Care Injured 40(S3):S44–S49

    Google Scholar 

  18. McMahon LA, Prendergast PJ, Campbell VA (2008) A comparison of the involvement of p38, ERK1/2 and PI3K in growth factor-induced chondrogenic differentiation of mesenchymal stem cells. Biochem Biophys Res Commun 18:990–995

    Article  Google Scholar 

  19. Vicky E, MacRae S, Ahmed F, Farquharson C (2007) IGF-I signalling in bone growth: Inhibitory actions of dexamethasone and IL-1b. Growth Horm IGF Res 7:435–439

    Google Scholar 

  20. Stavropoulou A, Halapas A, Sourla A (2009) IGF-1 expression in infarcted myocardium and MGF E peptide actions in rat cardiomyocytes in vitro. Mol Med 15:127–135

    Article  PubMed  CAS  Google Scholar 

  21. Raucci A, Bellosta P, Grassi R, Basilico C, Mansukhani A (2008) Osteoblast proliferation or differentiation is regulated by relative strengths of opposing signaling pathways. J Cell Physiol 215:442–451

    Article  PubMed  CAS  Google Scholar 

  22. Morshed S, Corrales L, Miclau T (2008) Outcome assessment in clinical trials of fracture-healing. J Bone Joint Surg 90:62–67

    Article  PubMed  Google Scholar 

  23. Mohan S (1993) Insulin-like growth factor binding proteins in bone cell regulation. Growth Reg 3:67–70

    CAS  Google Scholar 

  24. Circi E, Akpinar S, Tuncay IC (2009) Biomechanical and histological comparison of the influence of oestrogen deficient state on tendon healing potential in rats. Int Orthop 33:1461–1466

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by the National Nature Science Foundation of China (1032012, 30870609); Natural Science Foundation of Chongqing (CSTC2009BB4382CSTC2010BB5225); Foundation for Science & Technology Research Project of Chongqing (CSTC 2009AB517) and Project Foundation of Chongqing Municipal Education Committee (KJ091415).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yuanliang Wang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Deng, M., Zhang, B., Wang, K. et al. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. International Orthopaedics (SICOT) 35, 1099–1106 (2011). https://doi.org/10.1007/s00264-010-1141-2

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00264-010-1141-2

Keywords

Navigation