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

ABSTRACT: 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.

SUBMITTER: Yan B

PROVIDER: S-EPMC7269982 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:During orthodontic tooth movement (OTM) to therapeutically correct the position of misaligned teeth, thus improving oral health and quality of life, fibroblasts, macrophages, and other immune cells within the periodontal ligament (PDL), which connects a tooth to its surrounding bone, are exposed to compressive and tensile strain. While it is known that PDL fibroblasts are critically involved in the biological regulation of OTM by a mechanotransductively triggered release of cytokines, it is unclear whether macrophages also react to pressure and tension in a similar manner thus impacting on or mediating OTM. RAW264.7 macrophages were seeded onto conventional 6-well cell culture plates for pressure or on Bioflex plates for tension assays and preincubated for 24 h. For in vitro simulation of physiological orthodontic compressive or tensile strain for 2 h, 4 h, 24 h, and 48 h, glass discs (2 g/cm2) were placed or adherent macrophages isotropically stretched for 16%, respectively. We determined cell number, cytotoxicity, and gene/protein expression of Vegf-a/VEGF-A (macrophage-mediated angiogenesis), Mmp-8/9 (extracellular matrix reorganization), and Cox-2/PG-E2, Il-6/IL-6, and Tnf-α/TNF-α (proinflammatory mediators) by RT-qPCR and ELISA. Compressive but not tensile strain resulted in a significant reduction in cell number after only 2 h. Mmp-8 and Mmp-9 expression was significantly enhanced within 24 h of compressive and in part tensile strain. Significantly increased Vegf-a/VEGF-A expression was detected within 4 h of pressure, but not during application of tensile strain. Expression of proinflammatory mediators Cox-2/PG-E2, Il-6/IL-6, and Tnf-α/TNF-α was significantly increased as early as 2-4 h after application of compressive or tensile strain. Our results indicate that macrophages respond early on to compressive and tensile strain occurring during OTM with an enhanced gene expression of proinflammatory cytokines, which could affect PDL fibroblasts, osteoblasts, and immune cells triggering or enhancing the biological mechanisms and osteoclastogenesis underlying OTM.

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

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