title: Distraction osteogenesis-induced muscle fibrosis may not be associated with TGF-β1.
abstract: BACKGROUND
  Transforming growth factor-β 1 (TGF-β1) participates in the synthesis and deposition of collagen. It has been implicated in fibrosis of tendons in wound-healing models but has never been studied in muscles with respect to distraction osteogenesis.
  
  
  METHODS
  Using a rabbit model of distraction osteogenesis, we distracted the left tibias of 36 New Zealand white rabbits at 0.75 mm/d for 20 days. To determine whether suramin, an antagonist of TGF-β, could aid in the prevention of fibrosis, we injected it into the anterior tibialis muscle [12 rabbits received low-dose suramin (50 mg), 12 received high-dose suramin (100 mg), and 12 received sham injections]. Half of each group was killed at the end of distraction (day 24) and the other half at day 60. At the time of killing the rabbits, joint range of motion was measured, and strength and morphometric measures of the muscle were taken. Muscle was harvested and immunolabeled for TGF-β1. All findings were compared between study limbs and control (right) limbs.
  
  
  RESULTS
  The comparison failed to demonstrate improvements in the range of motion, and in strength or morphometric muscle development. Immunolabeling for TGF-β1 failed to show any staining in the intramuscular fibrosis. Paradoxically, muscle injected with high-dose suramin had the highest degree of fibrosis.
  
  
  CONCLUSIONS
  We conclude that TGF-β1 may not be the primary mediator of muscle fibrosis in distraction osteogenesis.
  
  
  CONCLUSIONS
  Injection of suramin may not prevent contracture formation after distraction osteogenesis.
authors.affiliation: Department of Pathology, University of Wisconsin School of Medicine and Public Health, Highland Avenue, Madison, WI 53215, USA. stephanie.koplin@aurora.org
authors.forename: Stephanie Ann
authors.initials: SA
authors.lastname: Koplin
authors.forename: Lillian
authors.initials: L
authors.lastname: Su
authors.forename: Shahriar
authors.initials: S
authors.lastname: Salamat
authors.forename: Jose
authors.initials: J
authors.lastname: Torrealba
authors.forename: James
authors.initials: J
authors.lastname: McCarthy
authors.forename: Jean
authors.initials: J
authors.lastname: Mitchell
authors.forename: Ronke
authors.initials: R
authors.lastname: Olabisi
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Noonan
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000473:pathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005355:Fibrosis; D007150:Immunohistochemistry; D018482:Muscle, Skeletal / Q000473:pathology*; D019857:Osteogenesis, Distraction / Q000009:adverse effects* / Q000379:methods; D011183:Postoperative Complications / Q000209:etiology; D011817:Rabbits; D016059:Range of Motion, Articular; D013498:Suramin / Q000008:administration & dosage / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D053773:Transforming Growth Factor beta1; D013498:Suramin