Schröder Agnes, Alefeld Annika, Forneck Anne, Spanier Gerrit, Deschner James, Proff Peter, Kirschneck Christian
Department of Orthodontics, University Medical Centre of Regensburg, Germany.
Department of Maxillo-Facial Surgery, University Medical Centre of Regensburg, Germany.
Eur J Orthod. 2022 Dec 1;44(6):659-668. doi: 10.1093/ejo/cjac013.
The endogenous hormone melatonin regulates the circadian rhythm and impacts on bone metabolism. As patient compliance to wear removable orthodontic appliances is generally higher at night, when melatonin release is increased, a boosting effect on tooth movement would be favourable for therapy, whereas an inhibiting effect would indicate daytime wear to be more therapy-effective. We hypothesize that melatonin has either a stimulating or impeding effect on the expression profile of periodontal ligament fibroblasts (PDLF) during simulated orthodontic compressive and tensile strain, which would suggest either an accelerating or inhibiting impact on orthodontic tooth movement in vivo.
PDLF were preincubated with melatonin for 24 h and then subjected to tensile or compressive strain to mimic tension and pressure sides in PDL. In addition, the selective melatonin MTNR1B-receptor antagonist 4P-PDOT was used. We investigated melatonin effects on collagen synthesis, expression of inflammatory and bone-remodelling genes/proteins by quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assays, and total collagen assays. PDLF-induced osteoclastogenesis was analysed in a coculture model by tartrate-resistant acid phosphatise (TRAP) staining.
Expression of melatonin receptors in PDLF was not affected by compressive strain. Melatonin increased expression of inflammatory factors and elevated collagen synthesis during mechanical strain. Melatonin showed no effects on OPG or RANKL expression without mechanical strain, but increased RANKL gene expression during compression.
Expression of melatonin receptors by PDLF enable them to detect fluctuating melatonin concentrations in the periodontal ligament. Melatonin increased collagen synthesis and expression of inflammatory mediators, but had no effect on genes involved in bone remodelling. Therefore, we suggest that melatonin has no accelerating effect on PDLF-induced osteoclastogenesis.
内源性激素褪黑素调节昼夜节律并影响骨代谢。由于患者夜间佩戴可摘矫治器的依从性通常较高，此时褪黑素释放增加，对牙齿移动产生促进作用将有利于治疗，而抑制作用则表明白天佩戴矫治器的治疗效果更佳。我们假设褪黑素在模拟正畸压缩和拉伸应变过程中，对牙周膜成纤维细胞（PDLF）的表达谱具有刺激或阻碍作用，这将提示其对体内正畸牙齿移动具有加速或抑制作用。
将PDLF与褪黑素预孵育24小时，然后施加拉伸或压缩应变以模拟牙周膜的张力侧和压力侧。此外，使用了选择性褪黑素MTNR1B受体拮抗剂4P-PDOT。我们通过定量实时聚合酶链反应、酶联免疫吸附测定和总胶原蛋白测定，研究了褪黑素对胶原蛋白合成、炎症和骨重塑基因/蛋白质表达的影响。在共培养模型中通过抗酒石酸酸性磷酸酶（TRAP）染色分析PDLF诱导的破骨细胞生成。
压缩应变不影响PDLF中褪黑素受体的表达。褪黑素在机械应变期间增加了炎症因子的表达并提高了胶原蛋白的合成。在没有机械应变的情况下，褪黑素对OPG或RANKL表达没有影响，但在压缩期间增加了RANKL基因的表达。
PDLF中褪黑素受体的表达使它们能够检测牙周膜中波动的褪黑素浓度。褪黑素增加了胶原蛋白的合成和炎症介质的表达，但对参与骨重塑的基因没有影响。因此，我们认为褪黑素对PDLF诱导的破骨细胞生成没有加速作用。
