Mechanical force-induced midpalatal suture remodeling in mice

Mechanical stress is an important epigenetic factor for regulating skeletal remodeling, and application of force can lead to remodeling of both bone and cartilage. Chondrocytes, osteoblasts and osteoclasts all participate and interact with each other in this remodeling process. To study cellular responses to mechanical stirnuli in a system that can be genetically manipulated, we used mouse midpalatal suture expansion in vivo. Six-week-old male C57BL/6 mice were subjected to palatal suture expansion by opening loops with an initial force of 0.56 N for the periods of 1, 3, 5, 7, 14 or 28 days. Periosteal cells in expanding sutures showed increased proliferation, with Ki67-positive cells representing 1.8 +/- 0.1% to 4.5 +/- 0.4% of total suture cells in control groups and 12.0 +/- 2.6% to 19.9 +/- 1.2% in experimental/expansion groups (P<0.05). Starting at day 1, cells expressing alkaline phosphatase and type I collagen were seen. New cartilage and bone formation was observed at the oral edges of the palatal bones at day 7; at the nasal edges only bone formation without cartilage appeared to occur. An increase in osteoclast numbers suggested increased bone remodeling, ranging from 60 to 160% throughout the experimental period. Decreased Saffranin O staining after day 3 suggested decreased proteoglycan content in the secondary cartilage. Micro-CT showed a significant increase in maxillary width at days 14 and 28 (from 2334 4 mu m to 2485 3 mu m at day 14 and from 2383 5 mu m to 2574 7 mu m at day 28, p<0.001). The suture width was increased at days 14 and 28, except in the oral third region at day 28 (from 48 5 mu m to 3614 mu m, p<0.05). Bone volume/total volume was significantly reduced at days 14 and 28 (50.2 +/- 0.7% vs. 68.0 +/- 3.7% and 56.5 +/- 1.0% vs. 60.9 +/- 1.3%, respectively, p<0.05), indicative of increased bone marrow space. These findings demonstrate that expansion forces across the midpalatal suture promote bone resorption through activation of osteoclasts and bone and cartilage formation via increased proliferation and differentiation of periosteal cells. Mouse midpalatal suture expansion would be useful in further studies of the ability of mineralized tissues to respond to mechanical stimulation. (c) 2007 Elsevier Inc. All rights reserved.