title: Mitogens are increased in the systemic circulation during bone callus healing.
abstract: The influence of mechanical tissue strain caused by flexible fracture fixation on the systemic occurrence of systemic mitogens during callus healing was investigated. For this purpose the mitogenic capacity and growth factor concentration of sera from patients undergoing fracture treatment were determined. Sera from 9 patients whose fractures had been stabilized by external fixation were collected before and during fracture treatment. The sera were added to cell culture media of the osteoblastic cell line SaOS-2. After 5-6 days cell proliferation was measured. Transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-I (IGF-I) concentrations were analyzed in serum samples from different healing stages.
  
  
  METHODS
  paired Wilcoxon-test. Sera from fracture patients decreased SaOS-2 proliferation in the first week after surgery (p<0.05) compared to sera obtained prior to surgery. In the fourth or fifth week proliferation increased significantly (p<0.03). The increased proliferation of the SaOS-2 cells was associated with elevated levels of TGF-beta and IGF-I (p<0.05). The higher mitogenic activity of sera suggests an increased level of circulating mitogens. In a previous study this increase had also been observed in patients during distraction osteogenesis treatment but not in patients with primary bone healing by a stable fixated plate. It is therefore assumed that their release from the fracture site is a consequence of mechanical stimulation by interfragmentary movement of fracture ends.
authors.affiliation: Institut für Unfallchirurgische Forschung und Biomechanik, Universität Ulm, Helmholtzstr. 14, 89081 Ulm, Germany. daniela.kaspar@medizin.uni-ulm.de
authors.forename: Daniela
authors.initials: D
authors.lastname: Kaspar
authors.forename: Cornelia
authors.initials: C
authors.lastname: Neidlinger-Wilke
authors.forename: Oliver
authors.initials: O
authors.lastname: Holbein
authors.forename: Lutz
authors.initials: L
authors.lastname: Claes
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
mesh_terms: D000328:Adult; D002146:Bony Callus / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D005260:Female; D005264:Femoral Fractures / Q000097:blood*; D005269:Femur / Q000293:injuries; D005592:Fracture Fixation; D017102:Fracture Healing / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D008934:Mitogens / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D019857:Osteogenesis, Distraction; D013977:Tibia / Q000293:injuries; D013978:Tibial Fractures / Q000097:blood*; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000097:blood; D053773:Transforming Growth Factor beta1
chemical_list: D008934:Mitogens; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D007334:Insulin-Like Growth Factor I