Activation of β-catenin signalling leads to temporomandibular joint defects

M. Wang, S. Li, W. Xie, J. Shen, H. J. Im, J. D. Holz, M. Wang, T. G.H. Diekwisch, D. Chen

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18 Scopus citations

Abstract

Despite extensive research in knee and hip osteoarthritis (OA), the underlying mechanism of temporomandibular joint (TMJ) disorder remains largely unknown. The purpose of this study was to determine whether the constitutive activation of β-catenin in the middle and deep layers of the articular cartilage can compromise the homeostasis of this tissue in the TMJ. Col2CreERT2 transgenic mice were bred with RosamT/mG reporter mice to determine Cre recombination efficiency. Col2CreERT2 mice were then crossed withβ-cateninflox(ex3)+ mice to generate β-catenin conditional activation mice, β-catenin(ex3)Col2ER. TMJ samples were harvested when the mice were 1-, 3- or 6-month-old and evaluated using histology, histomorphometry and immunohistochemistry. β-catenin(ex3)Col2ER mice were further crossed with Mmp13flox/flox and Adamts5-/- mice to generate (β-catenin(ex3)/Mmp13)Col2ER and β-catenin(ex3)Col2ER)/Adamts5-/- double mutant mice to investigate the role of Mmp13 and Adamts5 in the development of TMJ disorder. High levels of Cre-recombination were seen in Col2CreERT2;RosamT/mGmice. Progressive TMJ defects developed in 1-, 3- and 6-month-old β-catenin(ex3)Col2ER mice, as revealed by histology and histomorphometry. Results further demonstrated that the defects observed in β-catenin(ex3)Col2ER mice were significantly decelerated after deletion of the Mmp13 or Adamts5 gene in (β-catenin(ex3)/Mmp13)Col2ER or β-catenin(ex3)Col2ER/Adamts5-/- double mutant mice. In summary, we found that β-catenin is a critical gene in the induction of TMJ cartilage degeneration, and over-expressing β-catenin in TMJ cartilage leads to defects assembling an OA-like phenotype. Deletion ofMmp13 and Adamts5 in β-catenin(ex3)Col2ER mice ameliorates the development of TMJ defects. This study suggests that Mmp13 and Adamts5 could be potential therapeutic targets for the treatment of TMJ disorders.

Original languageEnglish
Pages (from-to)223-235
Number of pages13
JournalEuropean Cells and Materials
Volume28
DOIs
StatePublished - Oct 23 2014
Externally publishedYes

Keywords

  • Adamts5
  • MMP13
  • Osteoarthritis
  • Temporomandibular joint
  • β-catenin

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    Wang, M., Li, S., Xie, W., Shen, J., Im, H. J., Holz, J. D., Wang, M., Diekwisch, T. G. H., & Chen, D. (2014). Activation of β-catenin signalling leads to temporomandibular joint defects. European Cells and Materials, 28, 223-235. https://doi.org/10.22203/eCM.v028a15