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Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing

Knee Surgery, Sports Traumatology, Arthroscopy volume 20, pages 1907–1914 (2012)Cite this article

Abstract

Purpose

Achilles tendon ruptures are devastating and recover slowly and incompletely. There is a great demand for biomolecular therapies to improve recovery, yet little is understood about growth factors in a healing tendon. Here, the role of growth factors during tendon healing in a rat model and their reaction to single and multiple growth factor treatment are explored.

Methods

Rat tendons were transected surgically and resutured. The expression of bFGF, BMP-12, VEGF and TGF-β1 was assessed by immunohistochemical analysis one to 8 weeks after surgery. Paracrine effects of TGF-β1 or BMP-12 added by adenoviral transfer, as well as the effect of autologous conditioned serum (ACS) on growth factor expression, were evaluated.

Results

bFGF, BMP-12 and VEGF expression was highest 1 week after transection. bFGF and BMP-12 declined during the remaining period whereas VEGF expression persisted. TGF-β1 expression dramatically increased after 8 weeks. ACS treatment increased bFGF (P = 0.007) and BMP-12 (P = 0.004) expression significantly after 8 weeks. Also overall expression of bFGF, BMP-12 and TGF-β1 regardless of time point was significantly greater than controls with ACS treatment (P < 0.05). Both BMP-12 and TGF-β1 treatments had no significant effect. No effect was observed in VEGF with any treatment.

Conclusion

bFGF, BMP-12, VEGF and TGF-β1 are differentially expressed during tendon healing. Additional BMP-12 or TGF-β1 has no significant influence, whereas ACS generally increases expression of all factors except VEGF. Staged application of multiple growth factors may be the most promising biomolecular treatment.

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Abbreviations

ACS:

Autologous conditioned serum

bFGF:

Basic fibroblast growth factor, a.k.a. FGF-2

BMP:

Bone morphogenic protein

CDMP:

Cartilage-derived morphogenic protein

GDF:

Growth and differentiation factor

IGF-1:

Insulin-like growth factor 1

PDGF:

Platelet-derived growth factor

TGF-β1:

Transforming growth factor beta 1

VEGF:

Vascular endothelial growth factor

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Authors and Affiliations

  1. Orthopädische Klinik, Behandlungszentrum Bewegungsapparat, Universität Basel, Spitalstrasse 21, 4031, Basel, Switzerland

    Patricia E. Heisterbach, Atanas Todorov & Martin Majewski

  2. Center for Molecular Orthopaedics, Harvard Medical School, Boston, MA, USA

    Rudolf Flückiger & Christopher H. Evans

Authors
  1. Patricia E. Heisterbach
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  2. Atanas Todorov
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  3. Rudolf Flückiger
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  4. Christopher H. Evans
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  5. Martin Majewski
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Corresponding author

Correspondence to Martin Majewski.

Additional information

Patricia E. Heisterbach and Atanas Todorov are equally contributing first authors.

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Heisterbach, P.E., Todorov, A., Flückiger, R. et al. Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing. Knee Surg Sports Traumatol Arthrosc 20, 1907–1914 (2012). https://doi.org/10.1007/s00167-011-1772-x

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  • DOI: https://doi.org/10.1007/s00167-011-1772-x

Keywords

  • Growth factors
  • Tendon healing
  • Biological repair
  • Animal model