Local administration of high-dose diabetes medicine exendin-4 inhibits orthodontic tooth movement in mice

Wei Ren Shen, Hideki Kitaura, Jiawei Qi, Saika Ogawa, Fumitoshi Ohori, Takahiro Noguchi, Aseel Marahleh, Yasuhiko Nara, Pramusita Adya, Itaru Mizoguchi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)


Objectives: To investigate the effects of exendin-4 on orthodontic tooth movement distance, root resorption, and expression levels of osteoclast-related cytokines in a mouse model. Materials and Methods: A 10-g NiTi coil spring was placed between the anterior alveolar bone and upper left first molar of 8-week-old male C57BL/6 mice. Twenty microliters of exendin-4 solution (containing 0.2 μg, 4 μg, or 20 μg exendin-4) or phosphate-buffered saline (PBS) were injected on the buccal side of the upper left first molar at 2-day intervals (4 mice per group). Mice were sacrificed on day 12; silicone impressions were taken to record tooth movement distance. The left maxillae of the PBS and 20 lg exendin-4 groups were also excised for histological analysis and quantitative reverse transcription polymerase chain reaction analysis. Results: Orthodontic tooth movement distance was smaller in the 20 lg exendin-4 group than in the PBS group (P < .01). Compared with the PBS group, the 20 lg exendin-4 group showed lower osteoclast number (P < .05), odontoclast number (P <.05), and root resorption surface percentage (P < .05). Relative to maxillae with PBS injections, maxillae with 20 lg exendin-4 injections had lower receptor activator of nuclear factor kappa-B ligand (RANKL) mRNA expression (P <.05), TNF-a mRNA expression (P < .05), and RANKL/osteoprotegerin (OPG) ratio (P < .01). There were no differences in the expression of OPG mRNA. Conclusions: Exendin-4 inhibits orthodontic tooth movement. Therefore, additional attention is needed for orthodontic patients who receive exendin-4 for diabetes treatment. GLP-1 receptor may be a treatment target for patients with severe root resorption.

Original languageEnglish
Pages (from-to)111-118
Number of pages8
JournalAngle Orthodontist
Issue number1
Publication statusPublished - Jan 2021
Externally publishedYes


  • Diabetes
  • Exendin-4
  • GLP-1
  • Orthodontic tooth movement
  • Osteoclast


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