title: Matrix metalloproteinases and their inhibitors in bone remodelling following distraction osteogenesis of the sheep mandible.
abstract: OBJECTIVE
  Matrix metalloproteinases (MMPs), together with their tissue inhibitors (TIMPs), are responsible for the controlled degradation of collagen and other matrix substrates in bone and other tissues. This study evaluated the expression of MMPs and TIMPs in bony remodelling in a bilateral sheep mandible model up to 12 months following lengthening by distraction osteogenesis.
  
  
  METHODS
  Sheep mandibles were harvested 3, 6, 9 or 12 months following lengthening by bilateral mandibular distraction (1 mm/day for 20 days). Undistracted sheep mandibles were used as controls. The tissues underwent routine histology and immunohistochemical staining with monoclonal antibodies specific to MMPs 1-3 and TIMP-1, 2. Matrix and cell staining was assessed using a semi-quantitative analysis.
  
  
  RESULTS
  Matrix metalloproteinases and their tissue inhibitors (TIMPs) expression levels were marked at 3 months and decreased thereafter becoming similar to undistracted controls by 12 months. The histologic development of mature lamellar cortical bone was similar to undistracted controls by 9 months following distraction.
  
  
  CONCLUSIONS
  A temporal expression of MMPs and TIMPs was found in distraction osteogenesis. MMPs and TIMPS may, in part, reflect the state of bony remodelling following mandibular lengthening by distraction osteogenesis. Matrix metalloproteinases and TIMP expression were comparable to undistracted controls by 12 months, suggesting that equilibrium had been achieved and that bony relapse is unlikely.
authors.affiliation: University of New South Wales, Prince of Wales of Hospital, Division of Surgery, Randwick, Australia.
authors.forename: Damian D
authors.initials: DD
authors.lastname: Marucci
authors.forename: Yan
authors.initials: Y
authors.lastname: Yu
authors.forename: James
authors.initials: J
authors.lastname: McTavish
authors.forename: S
authors.initials: S
authors.lastname: Fiona Bonar
authors.forename: Michael D
authors.initials: MD
authors.lastname: Poole
authors.forename: William R
authors.initials: WR
authors.lastname: Walsh
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000201:enzymology; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000201:enzymology*; D007150:Immunohistochemistry; D008334:Mandible / Q000201:enzymology / Q000601:surgery*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis*; D019647:Oral Surgical Procedures; D010006:Osteoblasts / Q000201:enzymology; D010011:Osteocytes / Q000201:enzymology; D019857:Osteogenesis, Distraction; D012756:Sheep; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020782:Matrix Metalloproteinases