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, Shin‐ya

doi:10.3892/mmr.2017.7012

Cited by 23 publications

(21 citation statements)

References 53 publications

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“…Thermal stimuli were delivered to the forearm for 5 s while we recorded high-density EEG. The rationale for stimulating the subject's forearm rather than jaw, was to avoid potential between group differences that are focal to the jaw area in orofacial pain including lower pain thresholds in the masseter and anterior temporalis muscles (Farella et al, 2000; Hansdottir and Bakke, 2004), elevated levels of IL-6, IL-7, IL-8 and IL-13 in the masseter muscle (Louca Jounger et al, 2017), and elevated levels of elastin-derived peptides and IL-6 in the synovial fluid (Kaneyama et al, 2002; Kobayashi et al, 2017). EEG data were analyzed using time-frequency analysis, source-localization analysis, and measure projection analysis (MPA) (Bigdely-Shamlo et al, 2013), which together allowed us to characterize neuronal activity at different frequency bands in source space.…”

Section: Introductionmentioning

confidence: 99%

Altered neural oscillations within and between sensorimotor cortex and parietal cortex in chronic jaw pain

Wang

Misra²,

et al. 2019

NeuroImage: Clinical

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Pain perception is associated with priming of the motor system and the orienting of attention in healthy adults. These processes correspond with decreases in alpha and beta power in the sensorimotor and parietal cortices. The goal of the present study was to determine whether these findings extend to individuals with chronic pain. Individuals with chronic jaw pain and pain-free controls anticipated and experienced a low pain or a moderate pain-eliciting heat stimulus. Although stimuli were calibrated for each subject, stimulus temperature was not different between groups. High-density EEG data were collected during the anticipation and heat stimulation periods and were analyzed using independent component analyses, EEG source localization, and measure projection analyses. Direct directed transfer function was also estimated to identify frequency specific effective connectivity between regions. Between group differences were most evident during the heat stimulation period. We report three novel findings. First, the chronic jaw pain group had a relative increase in alpha and beta power and a relative decrease in theta and gamma power in sensorimotor cortex. Second, the chronic jaw pain group had a relative increase in power in the alpha and beta bands in parietal cortex. Third, the chronic jaw pain group had less connectivity strength in the beta and gamma bands between sensorimotor cortex and parietal cortex. Our findings show that the effect of chronic pain attenuates rather than magnifies neural responses to heat stimuli. We interpret these findings in the context of system-level changes in intrinsic sensorimotor and attentional circuits in chronic pain.

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Section: Introductionmentioning

confidence: 99%

Altered neural oscillations within and between sensorimotor cortex and parietal cortex in chronic jaw pain

Wang

Misra²,

et al. 2019

NeuroImage: Clinical

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“…Our data show that VGVAPG peptide did not increase ROS production and induce caspase-1 activation and cell proliferation in all studied concentrations and time intervals in 3T3-L1 cell line. To date, previous studies have shown that EDPs and/or VGVAPG peptide increase the production and/or secretion inflammatory markers such as IL-1α, IL-1β, and IL-6 in ligamentum flavum cells, synovial cells, and melanoma cell lines [ 63 – 65 ]. On the other hand, our previous studies show that VGVAPG peptide increases the expression of PPARγ and decreases the expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and production of IL-1β in mouse astrocytes in a PPARγ-dependent manner, which suggest that the effect of VGVAPG is tissue dependent [ 31 , 66 ].…”

Section: Discussionmentioning

confidence: 99%

Elastin-derived peptide VGVAPG decreases differentiation of mouse embryo fibroblast (3T3-L1) cells into adipocytes

et al. 2020

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Elastin is a highly elastic protein present in connective tissue. As a result of protease activity, elastin hydrolysis occurs, and during this process, elastin-derived peptides (EDPs) are released. One of the constitutively repeating elastin and EDP building sequences is the hexapeptide VGVAPG. Therefore, the aim of our research was to define the effect of VGVAPG peptide on adipogenesis in a mouse 3T3-L1 cell line. 3T3-L1 cells were differentiated according to a previously described protocol and exposed to increasing concentrations of VGVAPG or VVGPGA peptide. The obtained results showed that VGVAPG peptide does not stimulate reactive oxygen species (ROS) production, caspase-1 activation, and 3T3-L1 cell proliferation. In the second part of the experiments, it was proved that VGVAPG peptide decreased lipid accumulation as measured by oil red O staining, which was confirmed by the profile of increased expression markers of undifferentiated preadipocytes. In our experiments, 10 nM VGVAPG added for differentiating to adipocytes increased the expression of Pref-1, serpin E1, and adiponectin as compared to rosiglitazone (PPARγ agonist)-treated group and simultaneously decreased the expression of VEGF and resistin as compared to the rosiglitazone-treated group. The obtained results show that VGVAPG peptide sustains 3T3 cells in undifferentiated state.

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“…These results highlight the potential role of cytokines in TMJD pathogenesis. Our previous study showed that IL-6 expression in the synovial fluid obtained from patients with TMJD was significantly correlated with the two clinical parameters of TMJ locking and pain/jaw function based on a visual analogue scale (VAS) ( 13 ). Additionally, the concentration of elastin-digested peptides in the synovial fluid of patients with TMJD was significantly associated with the TMJ locking duration, the VAS and IL-6 expression ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Our previous study showed that IL-6 expression in the synovial fluid obtained from patients with TMJD was significantly correlated with the two clinical parameters of TMJ locking and pain/jaw function based on a visual analogue scale (VAS) ( 13 ). Additionally, the concentration of elastin-digested peptides in the synovial fluid of patients with TMJD was significantly associated with the TMJ locking duration, the VAS and IL-6 expression ( 13 ). In vitro , elastin-digested peptides act on human TMJ synovial cells to promote IL-6 upregulation and MMP-12 (an elastin-degrading enzyme) ( 13 ).…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, the concentration of elastin-digested peptides in the synovial fluid of patients with TMJD was significantly associated with the TMJ locking duration, the VAS and IL-6 expression ( 13 ). In vitro , elastin-digested peptides act on human TMJ synovial cells to promote IL-6 upregulation and MMP-12 (an elastin-degrading enzyme) ( 13 ). These findings suggest an inflammation model in the TMJ where elastin is degraded by a harmful mechanical stimulus, and the degradation products induce a pro-inflammatory cascade and increase the expression of MMP-12.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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

Cited by 23 publications

References 53 publications

Altered neural oscillations within and between sensorimotor cortex and parietal cortex in chronic jaw pain

Altered neural oscillations within and between sensorimotor cortex and parietal cortex in chronic jaw pain

Elastin-derived peptide VGVAPG decreases differentiation of mouse embryo fibroblast (3T3-L1) cells into adipocytes

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

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