Assessment of cell proliferation during mandibular distraction osteogenesis in the maturing rat

Introduction: The cellular mechanisms controlling distraction osteogenesis are not well understood. The purpose of this study was to examine the role of cell proliferation in the regulation of mandibular distraction osteogenesis. Methods: Unilateral mandibular ramus osteotomies were performed on 125 3-month-old Sprague-Dawley rats. The rats were randomized into 4 distraction rate groups and distracted for 5 days after 3-day latency. Rats (7 or 8 from each rate group) were killed at 4 time points. The rats received 5-bromo-2-deoxyuridine (BrdU) injections (40 mg per kilogram, i.p.) at day 3 (end of latency). Results: Both intramembranous and endochondral ossification was seen in the osteogenesis area. BrdU+ mesenchymal progenitor cells were significantly higher at day 10 (P <.05) and were found most numerously around the sagittal middle portion of the gap (P <.01). The greatest numbers of BrdU+ osteocytes were seen at day 38 (P <.05). Both BrdU+ osteoclasts and chondrocytes peaked at day 24. Conclusions: Mesenchymal progenitor cells are mostly recruited in the early consolidation period, but they decrease in the middle and late consolidation periods during mandibular distraction osteogenesis. The rapid rate might suppress or sustain the prolifereation and differentiation of mesenchymal progenitor cells during mandibular distraction osteogenesis. BrdU+ cells can survive throughout the entire experimental period of 5 weeks.