Regulation of DMP-1 Gene in Osteocytes during Distraction Osteogenesis

Distraction Osteogenesis (DO) enables lengthening of bones by gradually applying tensile strain across an osteotomy site where new bone is formed between the two bony segments. This project focused on an important protein in bone metabolism, dentin matrix protein-1 (DMP-1), shown to be involved in mineralization of bone, osteocyte signaling and during mechanical loading of bone. Objectives: To examine the time course of regulation and the effects of age and rate of distraction on DMP-1 expression during DO. Methods: Male Sprague-Dawley rats, either growing (one month old) or mature (three months old), underwent unilateral mandibular osteotomy. After a three day latent period, the bone segments were distracted for five days at one of four different rates (0, 0.2, 0.4, and 0.6 mm per day). The animals were sacrificed at 3, 6, 10, 24, and 38 days. Sections of treated hemi-mandibles were used for in situ hybridization for DMP-1 mRNA. The percent of parasurgical osteocytes expressing DMP-1 was determined by histomorphometry. Results: DMP-1 expression was regulated in a time-dependent manner (p < .001). Mean percent DMP-1 expression started at moderate levels (8.5%) during the latency phase (day 3), increased to high levels (14.1%) during the mid-distraction phase (day 6), peaked (16.4%) during the early consolidation phase (day 10), and declined to low levels 4.7% and 2.5% during the late consolidation phase (day 24) and the remodeling phase (day 38), respectively. The age of the animals and rate of distraction did not significantly alter DMP-1 expression (p = .69 and p = .296, respectively) . Conclusions: DMP-1 mRNA expression in parasurgical osteocytes was regulated in a time-dependent manner during DO and the expression levels were closely related to the biological stages of the process.