Systemic melatonin application increases bone formation in mandibular distraction osteogenesis

Abstract This study aimed to investigate the effects of different doses of systemic melatonin application on new bone formation during mandibular distraction osteogenesis (DO) in rats. Mandibular DO was performed on 30 adult female Sprague-Dawley rats, which were randomly divided into three groups: control group (CNT), melatonin dose 1 (MLT-D1), and melatonin dose 2 (MLT-D2). A five-day latent waiting period and a ten-day distraction phase followed the surgery. After the surgery, rats from the MLT-D1 and MLT-D2 groups received 25 and 50 mg/kg melatonin, respectively, at 7, 14, 21, 28, and 35 days. The animals were euthanised 28 days after distraction, i.e. at 43 days after surgery. Histological and histomorphometric analyses revealed that the distracted bone area was completely filled with new bone formation in all three groups. The MLT-D2 group exhibited the most new bone formation, followed by MLT-D1 and CNT. The melatonin groups had more osteoclasts than the CNT (p < 0.05). The number of osteoblasts was higher in the melatonin groups than in the CNT group, and the MLT-D2 had more osteoclasts than the MLT-D1 group (p < 0.05). Finally, the osteopontin (OPN) and vascular endothelial growth factor (VEGF) levels were higher in the melatonin groups than in the CNT group, and the MLT-D2 had higher OPN and VEGF levels than the MLT-D1 (p < 0.05). This study suggests that systemic melatonin application could increase new bone formation in DO.

Abstract 本研究旨在探究不同剂量全身应用褪黑素对大鼠下颌骨牵张成骨（mandibular distraction osteogenesis, DO）过程中新骨形成的影响。选取30只成年雌性斯普拉格-道利（Sprague-Dawley）大鼠，实施下颌骨牵张成骨术，随后将其随机分为三组：对照组（CNT）、褪黑素低剂量组（MLT-D1）与褪黑素高剂量组（MLT-D2）。术后依次开展5天的潜伏期与10天的牵张期。术后第7、14、21、28及35天，MLT-D1组与MLT-D2组大鼠分别予以25 mg/kg与50 mg/kg剂量的褪黑素。于牵张结束后28天，即术后43天，处死所有实验动物。组织学与组织形态计量学分析结果显示，三组大鼠的牵张骨区域均完全被新生骨组织填充。其中MLT-D2组新生骨形成量最多，其次为MLT-D1组与对照组（CNT）。褪黑素处理组的破骨细胞数量显著高于对照组（p < 0.05）；成骨细胞数量同样高于对照组，且MLT-D2组破骨细胞数量多于MLT-D1组（p < 0.05）。此外，褪黑素处理组的骨桥蛋白（osteopontin, OPN）与血管内皮生长因子（vascular endothelial growth factor, VEGF）表达水平均高于对照组，且MLT-D2组的OPN与VEGF水平显著高于MLT-D1组（p < 0.05）。本研究表明，全身应用褪黑素可促进下颌骨牵张成骨过程中的新生骨形成。