title: Effect of BMP-12, TGF-β1 and autologous conditioned serum on growth factor expression in Achilles tendon healing.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors: Orthopädische Klinik, Behandlungszentrum Bewegungsapparat, Universität Basel, Spitalstrasse 21, 4031, Basel, Switzerland.
authors: Patricia E
authors: PE
authors: Heisterbach
authors: Atanas
authors: A
authors: Todorov
authors: Rudolf
authors: R
authors: Flückiger
authors: Christopher H
authors: CH
authors: Evans
authors: Martin
authors: M
authors: Majewski
mesh_terms: D000125:Achilles Tendon / Q000187:drug effects / Q000293:injuries* / Q000502:physiology; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001804:Blood Transfusion, Autologous; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D018014:Gene Transfer Techniques; D055412:Growth Differentiation Factors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D007150:Immunohistochemistry; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D012421:Rupture / Q000188:drug therapy / Q000378:metabolism; D044967:Serum; D013708:Tendon Injuries / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; C499472:Gdf7 protein, rat; D055412:Growth Differentiation Factors; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D016222:Fibroblast Growth Factor 2