Effects of the multifunctional hormone leptin on orthodontic tooth movement in rats

This study aims to investigate the effects of leptin, which is a multifunctional hormone, on orthodontic tooth movement (OTM) and the underlying mechanism. Sprague-Dawley rat OTM models were established and divided into two groups with the administration of vehicle or leptin respectively. Stereomicroscope and microcomputed tomography were used to evaluate the amount of OTM. TRAP staining, immunohistochemical and immunofluorescence staining were used to detect osteoclasts and relative protein expressions. After treated with compression force, human periodontal ligament cells (hPDLCs) were co-cultured with human peripheral blood mononuclear cells (hPBMCs) with the presence or absence of leptin. Small interfering RNA (siRNA) was transfected to knock down the leptin receptor (LepR). The mRNA expressions of the targeted genes were evaluated by quantitative real-time polymerase chain reaction. We found that leptin receptors were expressed on both rat periodontal ligament cells and hPDLCs. OTM was significantly attenuated in the leptin-treated group comparing to the control group. The number of osteoclasts was reduced in the periodontal ligament tissues in vivo and in vitro co-cultured system when treated with leptin. The expression of RANKL was inhibited by leptin administration either in vivo and in vitro. Leptin administration also inhibited the force-induced up-regulation of RANKL expression in hPDLCs, which was rescued by LepR siRNA transfection. The osteoclastogenesis was attenuated by leptin administration which was reversed by the LepR siRNA transfection. Taken together, leptin was able to attenuate OTM by inhibiting osteoclastogenesis which can be attributed to the reduced expression of RANKL in the periodontal ligament. Leptin may possess the potential for reinforcing anchorage clinically.