Matrix metalloproteinases and their inhibitors in bone remodelling following distraction osteogenesis of the sheep mandible

Aim: 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. Methodology: 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.