title: Delayed fracture healing in growth differentiation factor 5-deficient mice: a pilot study.
abstract: BACKGROUND
  Growth differentiation factor-5 (GDF-5) is a key regulator of skeletogenesis and bone repair and induces bone formation in spinal fusions and nonunion applications by enhancing chondrocytic and osteocytic differentiation and stimulating angiogenesis. Elucidating the contribution of GDF-5 to fracture repair may support its clinical application in complex fractures.
  
  
  OBJECTIVE
  We therefore asked whether the absence of GDF-5 during fracture repair impaired bone healing as assessed radiographically, histologically, and mechanically.
  
  
  METHODS
  In this pilot study, we performed tibial osteotomies on 10-week-old male mice, stabilized by intramedullary and extramedullary nailing. Healing was assessed radiographically and histologically on Days 1 (n = 1 wild-type; n = 5 bp [brachopodism]), 5 (n = 3 wild-type; n = 3 bp), 10 (n = 6 wild-type; n = 3 bp), 14 (n = 6 wild-type; n = 6 bp), 21 (n = 6 wild-type; n = 6 bp), 28 (n = 7 wild-type; n = 6 bp), and 56 (n = 6 wild-type; n = 6 bp) after fracture. After 10 (n = 7 wild-type; n = 7 bp contralateral and n = 3 bp fractured tibiae), 14 (n = 6 wild-type; n = 6 bp), 21 (n = 6 wild-type; n = 6 bp), 28 (n = 6 wild-type; n = 3 bp), and 56 (n = 8 wild-type; n = 6 bp) days, the callus cross-sectional area was calculated. We characterized the mechanical integrity of the healing fracture by yield stress and Young's modulus at 28 (n = 6 wild-type; n = 3 bp) and 56 (n = 8 wild-type; n = 6 bp) days postfracture.
  
  
  RESULTS
  The absence of GDF-5 impaired cartilaginous matrix deposition in the callus and reduced callus cross-sectional area. After 56 days, the repaired bp fracture was mechanically comparable to that of controls.
  
  
  CONCLUSIONS
  Although GDF-5 deficiency did not compromise long-term fracture healing, a delay in cartilage formation and remodeling supports roles for GDF-5 in the early phase of bone repair.
  
  
  CONCLUSIONS
  Local delivery of GDF-5 to clinically difficult fractures may simulate cartilage formation in the callus and support subsequent remodeling.
authors: Cartilage Biology and Orthopaedics Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Department of Health and Human Service, Bethesda, MD, USA.
authors: Cynthia M
authors: CM
authors: Coleman
authors: Brooke H
authors: BH
authors: Scheremeta
authors: Amanda T
authors: AT
authors: Boyce
authors: Robert L
authors: RL
authors: Mauck
authors: Rocky S
authors: RS
authors: Tuan
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