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.

Combined Effects of Low‐Frequency Pulsed Electromagnetic Field and Melatonin on Ovariectomy‐Induced Bone Loss in Mice

“…Recently, Zheng et al [2020] demonstrated that the OPN expression level in human periodontal ligament stem cells (hPDLSCs) was downregulated by physiological MEL concentrations (1 pM-10 nM) and upregulated by the lowest pharmacological concentration (1 µM). Moreover, in a study on the mandibular distraction osteogenesis in rats, Acikan et al [2018] found that the OPN level was higher in the MEL groups with dosages of 25 and 50 mg/kg than in the control group, and the 50 mg/kg dose group had higher OPN levels than the 25 mg/kg dose group (P < 0.05). Although we used the pharmacological dose of MEL (50 mg/kg), there was no effect on the expression of OPN.…”

Rat bone marrow mesenchymal stem cells induced by rrPDGF-BB promotes bone regeneration during distraction osteogenesis

“…In order to promote the healing of distraction osteogenesis, researchers in various countries have conducted a large number of experimental studies on it. Akçay found that the systemic application of vitamin E can stimulate the formation of new bone in rabbit distraction osteogenesis, thereby shortening the treatment time ( Akçay et al, 2019 ); Acikan found that systemic application of melatonin can increase the formation of new bone in distraction osteogenesis ( Acikan et al, 2018 ); Altay found that oxytocin can promote bone metabolism, increase new bone formation and promote bone healing in the distraction area ( Altay et al, 2020 ); McDonald applied sclerostin antibody (Scl-Ab) in the rat model of distraction osteogenesis. The results showed that Scl-Ab treatment could promote bone formation and lead to bone regeneration with larger volume and higher strength.…”

Overview of Physical and Pharmacological Therapy in Enhancing Bone Regeneration Formation During Distraction Osteogenesis

“…In addition to this, melatonin can increase osteoblast proliferation and differentiation in vitro ( Dundar et al, 2016 ). The morphometrical and immunohistochemical outcomes in Acikan et al’ study uncovered a melatonin-induced dose-dependent increase for new bone regeneration in DO ( Acikan et al, 2018 ). In general, there are lacking of relevant experiments to demonstrate the association between Melatonin and DO.…”