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Mkx regulates the orthodontic tooth movement via osteoclast induction

Abstract

Introduction

The periodontal ligament (PDL) plays an important role in orthodontic tooth movement; however, the underlying molecular mechanism remains unclear. We have previously reported that the Mohawk homeobox (Mkx), a tendon-specific transcription factor, is expressed in the PDL and regulates its homeostasis.

Materials and methods

In the present study, we examined the role of Mkx in orthodontic tooth movement via bone remodeling induced by mechanical stimulation in Mkx-deficient rats, which are widely used as experimental animals for orthodontic force application. Orthodontic tooth movement of the maxillary first molar was performed in 7-week-old male Mkx-deficient rats (n = 4) and wild-type Wistar rats (n = 4) using coil springs for 14 days. Hematoxylin and eosin (H&E) staining and tartrate-resistant acid phosphatase (TRAP) staining were performed to evaluate morphological changes and osteoclasts. Furthermore, changes in the expression of receptor activator nuclear factor-kappa B ligand (RANKL) were demonstrated using immunostaining.

Results

The amount of tooth movement was significantly lower in Mkx-deficient rats than in wild-type rats. The number of TRAP-positive cells was suppressed in Mkx-deficient rats on the compression side.

Conclusion

Orthodontic tooth movement experiments in Mkx-deficient rats suggested that Mkx is involved in osteoclast induction at the alveolar bone surface on the compression side. This study reveals the possibility that Mkx plays a mechanosensory role in orthodontic tooth movement by inducing RANKL expression and osteoclastogenesis.

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Acknowledgements

This work was supported by the Japan Society for the Promotion of Science KAKENHI (Grant No. 20H05696, 18K19603 to H.A.), NIH grant (AR050631 to H.A.), and AMED‐CREST from AMED (Grant No. JP20gm0810008 to H.A.). We are also grateful to the staff of the Department of Systems BioMedicine at Tokyo Medical and Dental University (TMDU) for their support and discussion.

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Authors

Contributions

T.M. designed the study, analyzed the data, and wrote the manuscript; R.K. analyzed the data and provided critical advice on the data analysis and writing of the manuscript; T.K. and K.S. performed the histological examinations; T.C., T. Matsushima., R.N., H.T., K.T, L.Y., T. Matsumoto., and Y.K. provided critical advice; K.M. and H.A. conceptualized the study and was in charge of the overall direction and planning.

Corresponding authors

Correspondence to Keiji Moriyama or Hiroshi Asahara.

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The authors have no conflict of interest.

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Supplementary Information

Below is the link to the electronic supplementary material.

774_2021_1233_MOESM1_ESM.tiff

Supplementary file1 (TIFF 10263 KB) Figure S1. The distance between the incisors and first molars in rats. A. Schematic diagram and actual photo of the measurement area. I: Incisal tooth, M1: First molar. B. Quantification of the distance of I - M1 in each group (n = 4). Data represent the average and error bars represent the standard error (*p < 0.05, two-tailed Student’s t-test)

Supplementary file2 (TIFF 10263 KB) Figure S2. Negative control of RANKL.

774_2021_1233_MOESM3_ESM.tiff

Supplementary file3 (TIFF 10263 KB) Figure S3. Comparison of the number of RANKL-positive cells (n = 4). Data represent the average and error bars represent the standard error of mean (SEM). Two-way ANOVA test showed no significance

774_2021_1233_MOESM4_ESM.tiff

Supplementary file4 (TIFF 10263 KB) Figure S4. Immunohistochemistry of COL 1 A1 in the tooth root compression side after tooth movement. D: Dental, PDL: Periodontal ligament, AB: Alveolar bone

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Miyazaki, T., Kurimoto, R., Chiba, T. et al. Mkx regulates the orthodontic tooth movement via osteoclast induction. J Bone Miner Metab 39, 780–786 (2021). https://doi.org/10.1007/s00774-021-01233-2

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Keywords

  • Mohawk
  • PDL
  • Orthodontic tooth movement
  • Osteoclast
  • Rat