Open Access

Metalloelastase‑12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice

  • Authors:
    • Yoko Yamashita‑Futani
    • Rei Jokaji
    • Kazuhiro Ooi
    • Kazuhiko Kobayashi
    • Ioannis Kanakis
    • Ke Liu
    • Shuichi Kawashiri
    • George Bou‑Gharios
    • Hiroyuki Nakamura
  • View Affiliations

  • Published online on: April 1, 2021     https://doi.org/10.3892/br.2021.1427
  • Article Number: 51
  • Copyright: © Yamashita‑Futani et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Temporomandibular joint dysfunction (TMJD) is characterised by clinical symptoms involving both the masticatory muscles and the temporomandibular joint (TMJ). Disc internal derangement and osteoarthritis (OA) are the most common forms of TMJD. Currently, the molecular process associated with degenerative changes in the TMJ is unclear. Our previous study showed that elastin‑digested peptides act on human TMJ synovial cells and lead to upregulation of interleukin‑6 (IL‑6) and metalloelastase‑12 (MMP‑12; an elastin‑degrading enzyme) in vitro. However, there is limited information regarding the involvement of elastin‑degradation by MMP‑12 in the processes of inflammatory responses and cartilage degradation in vivo. STR/Ort mice were used as a model of TMJ OA in the present study. Significant articular cartilage degeneration was observed starting at 20 weeks of age in the STR/Ort mice and this progressed gradually until 40 weeks, compared with the age‑matched CBA mice. Immunostaining analysis showed that MMP‑12 and IL‑6 were expressed in the chondrocytes in the superficial zones of the cartilage. Immunostaining also showed that aggrecanases [a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)‑4 and ADAMTS‑5] were expressed in the chondrocytes in the superficial zones of the cartilage. These findings suggest that an inflammatory and degradative process was initiated in the TMJ. Harmful mechanical stimuli, particularly pressure, may cause damage to the elastin fibres in the most elastin‑rich superficial layer of the articular cartilage. Elastin‑digested peptides are then generated as endogenous warning signals and they initiate a pro‑inflammatory cascade. This leads to upregulation of pro‑inflammatory mediators, such as IL‑6 and MMP‑12, which further trigger tissue damage resulting in elevated levels of elastin‑digested peptides. IL‑6 increases expression of the aggrecanases ADAMTS‑4 and ADAMTS‑5, following cartilage degradation. This leads to the establishment of a positive feedback loop and may result in chronic inflammation and cartilage degradation of the TMJ in vivo.
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June-2021
Volume 14 Issue 6

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Spandidos Publications style
Yamashita‑Futani Y, Jokaji R, Ooi K, Kobayashi K, Kanakis I, Liu K, Kawashiri S, Bou‑Gharios G and Nakamura H: Metalloelastase‑12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice. Biomed Rep 14: 51, 2021
APA
Yamashita‑Futani, Y., Jokaji, R., Ooi, K., Kobayashi, K., Kanakis, I., Liu, K. ... Nakamura, H. (2021). Metalloelastase‑12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice. Biomedical Reports, 14, 51. https://doi.org/10.3892/br.2021.1427
MLA
Yamashita‑Futani, Y., Jokaji, R., Ooi, K., Kobayashi, K., Kanakis, I., Liu, K., Kawashiri, S., Bou‑Gharios, G., Nakamura, H."Metalloelastase‑12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice". Biomedical Reports 14.6 (2021): 51.
Chicago
Yamashita‑Futani, Y., Jokaji, R., Ooi, K., Kobayashi, K., Kanakis, I., Liu, K., Kawashiri, S., Bou‑Gharios, G., Nakamura, H."Metalloelastase‑12 is involved in the temporomandibular joint inflammatory response as well as cartilage degradation by aggrecanases in STR/Ort mice". Biomedical Reports 14, no. 6 (2021): 51. https://doi.org/10.3892/br.2021.1427