Elastin‑derived peptides are involved in the processes of human temporomandibular disorder by inducing inflammatory responses in synovial cells

Kobayashi,Kazuhiko; Jokaji,Rei; Miyazawa‑Hira,Mayuko; Takatsuka,Shigeyuki; Tanaka,Akira; Ooi,Kazuhiro; Nakamura,Hiroyuki; Kawashiri,Shuichi

doi:10.3892/mmr.2017.7012

Elastin‑derived peptides are involved in the processes of human temporomandibular disorder by inducing inflammatory responses in synovial cells

Authors:
- Kazuhiko Kobayashi
- Rei Jokaji
- Mayuko Miyazawa‑Hira
- Shigeyuki Takatsuka
- Akira Tanaka
- Kazuhiro Ooi
- Hiroyuki Nakamura
- Shuichi Kawashiri
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Affiliations: Department of Oral and Maxillofacial Surgery, Kanazawa University Graduate School of Medical Science, Kanazawa, Ishikawa 920‑8640, Japan, Department of Oral and Maxillofacial Surgery, Public Central Hospital of Matto Ishikawa, Hakusan, Ishikawa 924-8588, Japan
Published online on: July 15, 2017 https://doi.org/10.3892/mmr.2017.7012
Pages: 3147-3154
Copyright: © Kobayashi 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 (TMD) is a collection of clinical symptoms that involve masticatory muscles and the temporomandibular joint (TMJ). Common symptoms include limited jaw motion and joint sound/pain, along with TMJ disc displacement. TMD is frequently associated with synovitis, a chronic inflammation of the synovium. Fibroblast‑like synovial cells have been identified to produce several inflammatory mediators and may have an important role in the progression of TMJ inflammation. Degradation of the extracellular matrix molecule elastin may lead to the release of bioactive peptides. The present study aimed to explore the role of elastin‑derived peptides (EDPs) in human temporomandibular disorders. Therefore, interleukin‑6 (IL‑6) expression in the synovial fluid obtained from patients with TMD correlated significantly with two clinical parameters, specifically TMJ locking and pain/jaw function on a visual analog scale (VAS). To the best of our knowledge, this is the first study to determine that the concentration of EDPs in synovial fluid from patients with TMD may also be significantly correlated with the duration of TMJ locking, the VAS score and IL‑6 expression. In vitro, EDPs act on human TMJ synovial cells to promote upregulation of IL‑6 and the elastin‑degrading enzyme matrix metalloproteinase‑12 (MMP‑12). The upregulation of IL‑6 and MMP‑12 expression by EDPs may be mediated through elastin‑binding proteins (EBP) and a protein kinase A signalling cascade. These findings suggest a model for inflammation in the TMJ where EDPs are generated by harmful mechanical stimuli, induce both a pro‑inflammatory cascade and increase expression of MMP‑12 through activation of the EBP signalling cascade. This may lead to further increases in EDP levels, establishing a positive feedback loop leading to chronic inflammation in the TMJ. Therefore, significantly elevated levels of EDPs and IL‑6 in the synovial fluid of the TMJ may be indicators of the pathological conditions of the joint.

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