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

Clin Oral Investig. 2020 Oct;24(10):3547-3557. doi: 10.1007/s00784-020-03225-4. Epub 2020 Feb 7.


Objective: 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).

Results: 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.

Conclusion: 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.

Keywords: Indian hedgehog; Mandibular condylar cartilage; Mandibular lateral shift; Proteoglycan 4; Transforming growth factor beta-1.

MeSH terms

  • Animals
  • Cartilage
  • Hedgehog Proteins
  • Malocclusion
  • Mandibular Condyle*
  • Rats


  • Hedgehog Proteins