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

Heisterbach, Patricia ; Todorov, Atanas ; Flückiger, Rudolf ; Evans, Christopher ; Majewski, Martin

In: Knee Surgery, Sports Traumatology, Arthroscopy, 2012, vol. 20, no. 10, p. 1907-1914

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    Summary
    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 8weeks 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 1week after transection. bFGF and BMP-12 declined during the remaining period whereas VEGF expression persisted. TGF-β1 expression dramatically increased after 8weeks. ACS treatment increased bFGF (P=0.007) and BMP-12 (P=0.004) expression significantly after 8weeks. 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