Orthodontic Tooth Movement in MicroRNA-29 Sponge Transgenic Mice

Orthodontic tooth movement (OTM) occurs when a mechanical load is applied to a tooth through an appliance. Changes in these adaptive responses to orthodontic force depend on activities of periodontal ligament cells, osteoblasts, osteocytes and osteoclasts, which are influenced by cellular expression of regulatory genes at the right location for a given time. This is a sophisticated process that involves bone resorption at the sites of pressure and bone deposition on the tension side with a tight regulation at post-transcriptional and post-translational stages. To gain an insight into mechanisms that regulate the tooth movement at a molecular level will lead to an effective approach for clinicians to improve orthodontic care. MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important regulators of post-transcriptional gene expression in osteoblastogenesis and osteoclastogenesis. Emerging evidence has indicated that specific miRNAs play a crucial role in osteoclastogenesis and osteoclast differentiation. In this study, we focus on the miR-29 family, which expresses in different patterns corresponding to different orientations of forces in human periodontal ligament cells. In addition, miR-29 family plays important roles in osteoblasts/clasts differentiation and functions. The aim of the study is to evaluate the tooth movement phenotype of miR-29 sponge mice (miR-29 underexpressor) and gain insights into the possible mechanisms of how miR-29 family plays a role in tooth movement via osteoclast function; and to study the histological change and cellular effects from miR-29 loss of function. The tooth movement was achieved using a 5-cN expansion spring on a mandibular first molar of miR-29 sponge mice. After 2 weeks, the distance of tooth movement was evaluated using Faxitron® radiograph and a standardized gauge in microcomputed tomogram, H&E and TRAP staining were performed to investigate the activity of osteoclasts during tooth movement. In addition, RT-realtime PCR was performed to evaluate the level of expression of miRNA in each animal. The average distance of tooth movement in the miR-29 sponge transgenic mice were significantly less than the one in the wildtype control mice. The expression of miR-29 family in the miR-29 sponge mice were 0.2-0.6 folds lower than the ones in the control mice. In addition, the numbers of osteoclasts in the miR-29 sponge mice were less than in the control mice. The findings of this study reveal a previously unknown realm that a miRNA can modulate OTM via osteoclast function