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Mechanoresponsive and lubricating changes of mandibular condylar cartilage associated with mandibular lateral shift and recovery in the growing rat

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The in vivo mechanoresponsive and lubricating changes of the mandibular condylar cartilage (MCC) associated with mandibular lateral shift (MLS) and recovery are poorly understood. Using growing rats, we investigated whether the expression of mechanoresponsive factors, including proteoglycan-4 (PRG4), Indian hedgehog (Ihh) and transforming growth factor-β1 (TGF-β1), would be affected by MLS. We also investigated whether these changes could recover to the control level after a 2-week treatment reversal (TR).

Materials and methods

The MLS appliances were placed for 2 or 4 weeks in 5-week-old rats and removed from 7-week-old rats in the TR group. The MCC was analysed histomorphometrically by toluidine blue staining. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of PRG4, Ihh, PTHrP (parathyroid hormone-related protein), TGF-β1, Matrix metallopeptidase 13 (MMP-13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5).


A thickened superficial layer and an enhanced expression of PRG4 were detected in MLS groups. PTHrP-Ihh expression correlated positively with the up-regulation of PRG4. TGF-β1 expression decreased in the early stage of MLS but recovered to the control level in the TR group. A significantly enhanced expression of MMP-13 in MLS groups was detected.


MLS treatment, which acted on the growth stage of rats, affected the morphology and expression of lubrication factor in the MCC. Elimination of this mechanical stimulus may help MCC recover to normal conditions.

Clinical relevance

Our study supports that the adaptive changes of MCC, which are caused by mandibular functional deviation, could be largely recovered by early treatment.

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This study was supported by Grant-in-Aid for Scientific Research (16 K11782, 18 K17245) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

Author information

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Wu Yang and Xiyuan Guo. The first draft of the manuscript was written by Wu Yang. The manuscript was revised by Ikuo Yonemitsu, Ippei Watari, Katarzyna Anna Podyma-Inoue, Tetsuro Watabe and Takashi Ono. All authors read and approved the final manuscript.

Correspondence to Ikuo Yonemitsu.

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Ethical approval

The experimental procedures described here were approved by the Institutional Animal Care and Use Committee (A2018-025C) and performed in accordance with the Animal Care Standards of Tokyo Medical and Dental University.

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The authors have no conflicts of interest.

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Written informed consent was obtained from all participants included in the study.

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Yang, W., Podyma-Inoue, K.A., Yonemitsu, I. et al. Mechanoresponsive and lubricating changes of mandibular condylar cartilage associated with mandibular lateral shift and recovery in the growing rat. Clin Oral Invest (2020). https://doi.org/10.1007/s00784-020-03225-4

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  • Mandibular condylar cartilage
  • Mandibular lateral shift
  • Proteoglycan 4
  • Indian hedgehog
  • Transforming growth factor beta-1