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Stimulation of bone growth factor synthesis in human osteoblasts and fibroblasts after extracorporeal shock wave application

  • Orthopaedic Surgery
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Archives of Orthopaedic and Trauma Surgery Aims and scope Submit manuscript

Abstract

Background

Nonunion is a common problem in Orthopedic Surgery. In the recent years alternatives to the standard surgical procedures were tested clinically and in vitro. Extracorporeal shock wave therapy (ESWT) showed promising results in both settings. We hypothesized that in target tissue cells from nonunions like fibroblasts and osteoblasts ESWT increases the release of bone growth factors.

Methods

Fibroblasts and osteoblasts were suspended in 3 ml cryotubes and subjected to 250/500 shock waves at 25 kV using an experimental electrohydraulic lithotripter. After ESWT, cell viability was determined and cells were seeded at 1 × 105 cells in 12 well plates. After 24, 48, and 72 h cell number was determined and supernatant was frozen. The levels of growth factors FGF-2 and TGF-β1 were examined using ELISA. A control group was treated equally without receiving ESWT.

Results

After 24 h there was a significant increase in FGF-2 levels (p < 0.05) with significant correlation to the number of impulses (p < 0.05) observed. TGF-β1 showed a time-dependent increase with a peak at 48 h which was not significantly different from the control group.

Conclusions

FGF-2, an important growth factor in new bone formation, was shown to be produced by human fibroblasts and osteoblasts after treatment with ESWT. These findings demonstrate that ESWT is able to cause bone healing through a molecular way by inducing growth factor synthesis.

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References

  1. Maier M, Steinborn M, Schmitz C et al (2000) Extracorporeal shock wave application for chronic plantar fasciitis associated with heel spurs: prediction of outcome by magnetic resonance imaging. J Rheumatol 27:2455–2462

    CAS  PubMed  Google Scholar 

  2. Ogden JA, Alvarez R, Levitt R et al (2001) Shock wave therapy for chronic proximal plantar fasciitis. Clin Orthop 387:47–59

    Article  PubMed  Google Scholar 

  3. Rompe JD, Schoellner C, Nafe B (2002) Evaluation of low-energy extracorporeal shock-wave application for treatment of chronic plantar fasciitis. J Bone Joint Surg Am 84:335–341

    Article  PubMed  Google Scholar 

  4. Rompe JD, Zoellner J, Nafe B (2001) Shock wave therapy versus conventional surgery in the treatment of calcifying tendinitis of the shoulder. Clin Orthop 387:72–82

    Article  PubMed  Google Scholar 

  5. Wang CJ, Ko JY, Chen HS (2001) Treatment of calcifying tendinitis of the shoulder with shock wave therapy. Clin Orthop 387:837–889

    Google Scholar 

  6. Maier M, Steinborn M, Schmitz C et al (2001) Extracorporeal shock-wave therapy for chronic lateral tennis elbow-prediction of outcome by imaging. Arch Orthop Trauma Surg 121:379–384

    Article  CAS  PubMed  Google Scholar 

  7. Buchbinder R, Green S, White M et al (2005) Shock wave therapy for lateral elbow pain (Cochrane Review). Cochrane Database Syst Rev 19(4):CD003524

    Google Scholar 

  8. Ikeda K, Tomita K, Takayama K (1999) Application of extracorporeal shock wave on bone: preliminary report. J Trauma 47:946–950

    Article  CAS  PubMed  Google Scholar 

  9. Rompe JD, Rosendahl T, Schollner C et al (2001) High-energy extracorporeal shock wave treatment of nonunions. Clin Orthop 387:102–111

    Article  PubMed  Google Scholar 

  10. Schaden W, Fischer A, Sailler A (2001) Extracorporeal shock wave therapy of nonunion or delayed osseous union. Clin Orthop 387:90–94

    Article  PubMed  Google Scholar 

  11. Wang CJ, Chen HS, Chen CE, Yang KD (2001) Treatment of nonunions of long bone fractures with shock waves. Clin Orthop 387:95–101

    Article  PubMed  Google Scholar 

  12. Maier M, Hausdorf J, Tischer T et al (2004) New bone formation by extracorporeal shock waves. Dependence of induction on energy flux density. Orthopäde 33(12):1401–1410

    Article  CAS  PubMed  Google Scholar 

  13. Wang FS, Wang CJ, Huang HJ et al (2001) Physical shock wave mediates membrane hyperpolarization and Ras activation for osteogenesis in human bone marrow stromal cells. Biochem Biophys Res Commun 287(3):648–655

    Article  CAS  PubMed  Google Scholar 

  14. Martini L, Giavaresi G, Fini M et al (2003) Effect of extracorporeal shock wave therapy on osteoblast like cells. Clin Orthop Relat Res Aug(413):269–280

  15. Chen YJ, Wurtz T, Wang CJ et al (2004) Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. J Orthop Res 22(3):526–534

    Article  CAS  PubMed  Google Scholar 

  16. Maier M, Averbeck B, Milz S et al (2003) Substance P and prostaglandin E2 release after shock wave application to the rabbit femur. Clin Orthop Relat Res Jan(406):237–245

  17. Lieberman JR, Daluiski A, Einhorn TA (2002) The role of growth factors in the repair of bone. Biology and clinical applications. J Bone Joint Surg Am 84-A(6):1032–1044

    PubMed  Google Scholar 

  18. Solchaga LA, Penick K, Porter JD, Goldberg VM, Caplan AI, Welter JF (2005) FGF-2 enhances the mitotic and chondrogenic potentials of human adult bone marrow-derived mesenchymal stem cells. J Cell Physiol 203:398

    Article  CAS  PubMed  Google Scholar 

  19. Canalis E, Centrella M, McCarthy T (1988) Effects of basic fibroblast growth factor on bone formation in vitro. J Clin Invest 81(5):1572–1577

    Article  CAS  PubMed  Google Scholar 

  20. Robey PG, Termine JD (1985) Human bone cells in vitro. Calcif Tissue Int 37(5):453–460

    Article  CAS  PubMed  Google Scholar 

  21. Rubin J, Rubin C, Jacobs CR (2006) Molecular pathways mediating mechanical signalling in bone. Gene 367:1–16

    Article  CAS  PubMed  Google Scholar 

  22. Skutek M, van Griensven M, Zeichen J et al (2001) Cyclic mechanical stretching modulates secretion pattern of growth factors in human tendon fibroblasts. Eur J Appl Physiol 86(1):48–52

    Article  CAS  PubMed  Google Scholar 

  23. Weiss S, Baumgart R, Jochum M (2002) Systemic regulation of distraction osteogenesis: a cascade of biochemical factors. J Bone Miner Res 17(7):1280–1289

    Article  CAS  PubMed  Google Scholar 

  24. Lean JM, Jagger CJ, Chambers TJ et al (1995) Increased insulin-like growth factor I mRNA expression in rat osteocytes in response to mechanical stimulation. Am J Physiol 268(2 Pt 1):E318–E327

    CAS  PubMed  Google Scholar 

  25. Lean JM, Mackay AG, Chow JW (1996) Osteocytic expression of mRNA for c-fos and IGF-I: an immediate early gene response to an osteogenic stimulus. Am J Physiol 270(6 Pt 1):E937–E945

    CAS  PubMed  Google Scholar 

  26. Kusnierczak D, Brocai DR, Vettel U et al (2000) Effect of extracorporeal shockwave administration on biological behavior of bone cells in vitro. Z Orthop Ihre Grenzgeb 138(1):29–33

    Article  CAS  PubMed  Google Scholar 

  27. Kaulesar Johannes EJ, Sukul DM, Bijma AM et al (1994) Effects of high energy shockwaves on normal human fibroblasts in suspension. J Surg Res 57:677–681

    Article  CAS  PubMed  Google Scholar 

  28. Dorotka R, Kubista B, Schatz KD et al (2003) Effects of extracorporeal shock waves on human articular chondrocytes and ovine bone marrow stromal cells in vitro. Arch Orthop Trauma Surg 123(7):345–348

    Article  CAS  PubMed  Google Scholar 

  29. Delius M, Adams G (1999) Shock wave permeabilization with ribosome inactivating proteins: a new approach to tumor therapy. Cancer Res 59(20):5227–5232

    CAS  PubMed  Google Scholar 

  30. Renz H, Rupp S, Basso N (2009) Effects of shock waves on chondrocytes and their relevance in clinical practice. Arch Orthop Trauma Surg 129(5):641–647

    Article  PubMed  Google Scholar 

  31. Pfeilschifter JI, Diel U, Pilz K et al (1993) Mitogenic responsiveness of human bone cells in vitro to hormones and growth factors decreases with age. J Bone Miner Res 8(6):707–717

    Article  CAS  PubMed  Google Scholar 

  32. Heersche JNM (2002) Characteristics of in vitro osteoblastic cell loading models. Bone 30(2):347–351

    Article  PubMed  Google Scholar 

  33. Goldring MB, Goldring SR (1990) Skeletal tissue response to cytokines. Clin Orthop Relat Res. Sep;(258):245–278

  34. Hofmann A, Ritz U, Hessmann MH et al (2008) Extracorporeal shock wave-mediated changes in proliferation, differentiation, and gene expression of human osteoblasts. J Trauma 65(6):1402–1410

    Article  PubMed  Google Scholar 

  35. Wang FS, Wang CJ, Sheen-Chen SM et al (2002) Superoxide mediates shock wave induction of ERK-dependent osteogenic transcription factor (CBFA1) and mesenchymal cell differentiation toward osteoprogenitors. J Biol Chem 277(13):10931–10937

    Article  CAS  PubMed  Google Scholar 

  36. Rompe JDCJ, Kirkpatrick K, Kullmer M et al (1998) Dose-related effects of shock waves on rabbit tendo Achillis A sonographic and histological study. J Bone Joint Surg Br 80(3):546–552

    Article  CAS  PubMed  Google Scholar 

  37. Yeaman LD, Jerome CP, McCullough DL (1989) Effects of shock waves on the structure and growth of the immature rat epiphysis. J Urol 141:670–674

    CAS  PubMed  Google Scholar 

  38. Mayer-Wagner S, Ernst J, Maier M, Chiquet M, Joos H, Muller PE, Jansson V, Sievers B, Hausdorf J (2010) The effect of high-energy extracorporeal shock waves on hyaline cartilage of adult rats in vivo. J Orthop Res 28(8):1050–1056

    Google Scholar 

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Acknowledgments

The authors indicate no potential conflicts of interests.

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Authors and Affiliations

  1. Orthopaedic Department, Campus Großhadern, Ludwig-Maximilians-University Munich, Marchioninistr. 15, 81377, Munich, Germany

    Joerg Hausdorf, Birte Sievers, Marcus Schmitt-Sody, Volkmar Jansson, Markus Maier & Susanne Mayer-Wagner

Authors
  1. Joerg Hausdorf
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  2. Birte Sievers
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  3. Marcus Schmitt-Sody
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  4. Volkmar Jansson
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  5. Markus Maier
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  6. Susanne Mayer-Wagner
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Corresponding author

Correspondence to Joerg Hausdorf.

Additional information

M. Maier practices occasionally as lecturer for Dornier.

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Hausdorf, J., Sievers, B., Schmitt-Sody, M. et al. Stimulation of bone growth factor synthesis in human osteoblasts and fibroblasts after extracorporeal shock wave application. Arch Orthop Trauma Surg 131, 303–309 (2011). https://doi.org/10.1007/s00402-010-1166-4

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  • DOI: https://doi.org/10.1007/s00402-010-1166-4

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