Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing
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- Heisterbach, P.E., Todorov, A., Flückiger, R. et al. Knee Surg Sports Traumatol Arthrosc (2012) 20: 1907. doi:10.1007/s00167-011-1772-x
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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.
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.
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.
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.
KeywordsGrowth factors Tendon healing Biological repair Animal model
Autologous conditioned serum
Basic fibroblast growth factor, a.k.a. FGF-2
Bone morphogenic protein
Cartilage-derived morphogenic protein
Growth and differentiation factor
Insulin-like growth factor 1
Platelet-derived growth factor
Transforming growth factor beta 1
Vascular endothelial growth factor