The dipeptide prolyl-hydroxyproline promotes cellular homeostasis and lamellipodia-driven motility via active ß1-integrin in adult tendon cells.

Collagen-derived hydroxyproline (Hyp)-containing peptides have a variety of biological effects on cells. These bioactive collagen peptides are locally generated by the degradation of endogenous collagen in response to injury. However, no comprehensive study has yet explored the functional links between Hyp-containing peptides and cellular behavior. Here, we show that the dipeptide prolyl-4-hydroxyproline (Pro-Hyp) exhibits pronounced effects on mouse tendon cells. Pro-Hyp promotes differentiation/maturation of tendon cells with modulation of lineage-specific factors and induces significant chemotactic activity in vitro. In addition, Pro-Hyp has profound effects on cell proliferation, with significantly upregulated extracellular signal-regulated kinase phosphorylation and extracellular matrix production and increased type I collagen network organization. Using proteomics, we have predicted molecular transport, cellular assembly and organization, and cellular movement as potential linked-network pathways that could be altered in response to Pro-Hyp. Mechanistically, cells treated with Pro-Hyp demonstrate increased directional persistence and significantly increased directed motility and migration velocity. They are accompanied by elongated lamellipodial protrusions with increased levels of active ß1-integrin-containing focal contacts, as well as reorganization of thicker peripheral F-actin fibrils. Pro-Hyp-mediated chemotactic activity is significantly reduced (p < 0.001) in cells treated with the mitogen-activated protein kinase kinase 1/2 inhibitor PD98059 or the α5ß1-integrin antagonist ATN-161. Furthermore, ATN-161 significantly inhibits uptake of Pro-Hyp into adult tenocytes. Thus, our findings document the molecular basis of the functional benefits of the Pro-Hyp dipeptide in cellular behavior. These dynamic properties of collagen-derived Pro-Hyp dipeptide could lead the way to its application in translational medicine.

Evaluation of factors related to morphological masseter muscle changes after preoperative orthodontic treatment in female patients with skeletal class III dentofacial deformities.

BACKGROUND: The purpose of the current study was to investigate factors related to morphological changes in the masseter muscle after preoperative orthodontic treatment in patients with skeletal class III dentofacial deformities for analysis of muscle changes and malocclusions. METHODS: Twenty female patients with dentofacial deformities were included in the study. Computed tomography was performed before and after preoperative orthodontic treatment, and the lengths, widths, and cross-sectional areas of the masseter muscles were measured. Changes in these parameters were evaluated, and factors related to changes in masseter muscle area after preoperative orthodontic treatment were analyzed. RESULTS: The lengths, widths, and areas of masseter muscles were significantly smaller after preoperative orthodontic treatment. Smaller masseter muscle area was significantly associated with changes in overbite and pretreatment values of SNA angle. CONCLUSIONS: Atrophy of the masseter muscle during preoperative orthodontic treatment was greater in patients with increased open bite due to improved dental compensation in patients with skeletal class III dentofacial deformities with maxillary retraction.

Relationship between pharyngeal airway depth and ventilation condition in mandibular setback surgery: A computational fluid dynamics study.

OBJECTIVES: This study aimed to determine the anteroposterior depth (APD) of the pharyngeal airway (PA) where post-operative PA obstruction was predicted, using computer fluid dynamics (CFD), in order to prevent obstructive sleep apnoea after mandibular setback surgery. SETTINGS AND SAMPLE POPULATION: Nineteen skeletal Class III patients (8 men; mean age, 26.7 years) who required mandibular setback surgery had computed tomography images taken before and 6 months after surgery. METHODS: The APD of each site of the four cross-sectional reference planes (retropalatal airway [RA], second cervical vertebral airway, oropharyngeal airway and third cervical vertebral airway) were measured. The Maximum negative pressure (Pmax) of the PA was measured at inspiration using CFD, based on a three-dimensional PA model. Intersite differences were determined using analysis of variance and the Friedman test with Bonferroni correction. The relationship between APD and Pmax was evaluated by Spearman correlation coefficients and non-linear regression analysis. RESULTS: The smallest PA site was the RA. Pmax was significantly correlated with the APD of the RA (rs  = .628, P < .001). The relationship between Pmax and the APD-RA was fitted to a curve, which showed an inversely proportional relationship of Pmax to the square of the APD-RA. Pmax substantially increased even with a slight reduction of the APD-RA. In particular, when the APD-RA was 7 mm or less, Pmax increased greatly, suggesting that PA obstruction was more likely to occur. CONCLUSIONS: The results of this study suggest that APD-RA is a useful predictor of good PA ventilation after surgery.

Comparison of Maximum Mouth Opening Following Mandibular Bilateral Sagittal Splitting Ramus osteotomies in Class III Females Using Two Different Osteosynthesis Methods.

BACKGROUND: Limitation of mouth opening is a common complaint following orthognathic surgery. OBJECTIVES: This investigation reports on the progress of maximum incisal opening following orthognathic surgery and compares the impact of two different osteosynthesis methods on mouth opening in female patients with Class III dentofacial deformities. METHODS: Forty cases of skeletal class III malocclusion were divided into twenty cases treated using the conventional single miniplate osteosynthesis method (P1) and twenty cases using the additional L-shaped miniplate osteosynthesis method (P2). No significant differences in pre-operative clinical status were detected between the P1 and P2 group, and all patients were managed with elastics in the post-operative period. Independent mouth opening exercises were initiated seven days after surgery, and inter-incisal distance was measured as maximum mouth opening (MMO) at 1 week, 2 weeks, and 1, 2, 3, 6 months. Statistical analysis was performed in order to analyse differences in MMO between the P1 and P2 groups (Prism 7 GraphPad software, San Diego, CA). Values of P < .05 were considered to be significant. RESULTS: MMO significantly increased from 2 weeks after surgery in both groups. The MMO of P2 was significantly larger than that of P1 in all experimental periods after surgery. MMO was statistically improved in P2 at 2 months after surgery, while MMO in P1 was significantly smaller than the pre-operative MMO, even at 6 months post-operative. A minimum MMO of 40 mm was achieved by all patients. CONCLUSION: L-shaped miniplate osteosynthesis was more useful for early limitation of mandibular opening improvement than conventional single miniplate osteosynthesis.

The pattern and spread of invasion can predict late cervical lymph node metastasis in early tongue squamous cell carcinoma.

To determine the predictive indexes of late cervical lymph node metastasis in early tongue squamous cell carcinoma (TSCC). We retrospectively analyzed the cases of 25 patients with stage I/II TSCC who had undergone surgical treatment without elective neck dissection. We evaluated the relationships between clinicopathologic factors and the occurrence of late cervical lymph node metastasis. Of the 25 cases, metastasis to the cervical lymph nodes was observed in nine cases (36.0%). The clinicopathological factors associated with late cervical lymph node metastasis were the mode of invasion (MOI, p = 0.032), depth of invasion (DOI, p = 0.004), and perineural invasion (PNI, p = 0.040). A multivariate analysis revealed that only the DOI was an independent predictor of late cervical lymph node metastasis. The combination of the DOI and MOI or the PNI and MOI was significantly correlated with late cervical lymph node metastasis (p = 0.004 and p = 0.012, respectively). Our findings suggest that combinations of the MOI, DOI, and PNI could be used as an index for predicting late cervical lymph node metastasis in early TSCC.

Intra-articular fracture of the mandibular condyle: a case report.

The authors describe a case of intra-articular fracture of the left mandibular condyle, successfully treated by the pumping technique in the upper and lower joint cavities, and show arthroscopic findings in these cavities. The patient was a 15-year-old boy whose maximum mouth opening was 30 mm. Computed tomography revealed a left intra-articular sagittal fracture of the condylar head. Aspiration of the hematoma in the upper and lower joint spaces was performed with ten pumping actions. In the upper and lower joint spaces, arthroscopic examination revealed the disappearance of the hematoma. The patient continued opening, protrusive, and lateral excursive exercises. One month after the surgery, the maximal interincisal distance was improved to 45 mm with straight opening. In the case presented, mouth-opening exercises, along with the pumping technique for treatment of an intraarticular fracture of the mandibular condyle, allowed satisfactory and stable results in the improvement of limited mouth movement.

Therapy outcome measures in temporomandibular disorder: a scoping review.

OBJECTIVES: Therapy outcome measures (TOMs) in temporomandibular disorders (TMDs) have not been systematically evaluated. We systematically explored the main TOM assessment methods for TMD TOMs used in previous studies. DESIGN: Scoping review. DATA SOURCES: According to Preferred Reporting Items for Systematic reviews and Meta-Analysis extension for Scoping Review reporting guidelines, we systematically searched five key databases (MEDLINE/PubMed, Web of Science, Embase, Epistemonikos and ClinicalTrials) and thoroughly scanned relevant grey literature using Medical Subject Headings, Emtree and index terms. ELIGIBILITY CRITERIA: We considered primary research papers published from January 2010 to December 2020 that included patients with TMD aged ≥18 years, diagnosed according to the Diagnostic Criteria for Temporomandibular Disorders. DATA EXTRACTION AND SYNTHESIS: Four reviewers extracted general information and information on study design and setting, target, interventions, and outcome type. RESULTS: One hundred and seventy-two of the 3726 screened articles (3704 by search engines and 22 manually) were included. The TOMs analysed included pain (n=161 articles), maximal mouth opening (MMO) (91), jaw function (32), jaw movement (26), joint sound (16), quality of life (QOL) (15), depression/anxiety (14), oral QOL (10) or others (30). Evaluation periods were <4 weeks (111), <8 weeks (62), <12 weeks (59), >12 weeks (75) or 'not mentioned' (12). Pain outcomes (229) included general pain (115), tenderness (45), pain during functioning (44), resting pain (16) and others (8). Pain outcome evaluation methods included Visual Analogue Scale (VAS; 121), Numerical Rating Scale (21) and other methods (21). Pain outcome indicators were binary (10) or continuous (158); only five studies reported the least significant difference in treatment efficacy. MMO evaluation using painless methods (19) and jaw function evaluation using methods assessing mandibular movement range (23) were the most frequent. CONCLUSIONS: TMD TOMs are diverse; the major outcomes were pain, MMO, jaw function and jaw movement. Most pain outcomes are evaluated by VAS Score changes.

Factors related to oxygen desaturation index during sleep 7 days after bilateral sagittal splitting ramus osteotomy in patients without previous obstructive sleep apnea.

PURPOSE: The incidence of obstructive sleep apnea (OSA) immediately after surgery in patients with dentofacial deformities without previous OSA remains unknown. We aimed to perioperatively evaluate factors associated with oxygen desaturation index (ODI) during sleep, 7 days after bilateral splitting ramus osteotomy (BSSRO) in patients without previous OSA. METHODS: Fifty-one patients (15 males, 36 females) with dentofacial deformities, scheduled to undergo BSSRO, were included. Polysomnography was performed before orthognathic surgery. Perioperative OSA was evaluated with peripheral arterial tonometry on the day of surgery and 1, 2, 3, 4, and 7 days postoperatively. Rapid eye movement (REM) sleep periods and the ODI were measured. Factors associated with perioperative ODI after surgery were statistically analyzed. RESULTS: REM sleep periods were significantly decreased on the day of surgery and significantly increased at 4 and 7 days postoperatively, compared to the preoperative period. ODI increased on the day of surgery, decreased after 1 day, and increased again at 4 and 7 days postoperatively. ODI on the day of surgery was significantly increased due to increased preoperative ODI, overjet, and SN-MP angle and decreased SNA and SNB angle. ODI at 7 days postoperatively was significantly increased due to increased REM sleep periods and decreased SN-MP and gonial angle. ODI was increased in response to REM sleep periods 7 days after BSSO. CONCLUSION: Airway management in patients with dentofacial deformity should be given more attention by preoperative assessment for OSA, even in the absence of previous OSA, until 7 days postoperatively due to REM rebound.

Evaluation of Rhythmic Masseter Muscle Activity during Sleep and Awake in Patients with Dentofacial Deformity.

Objectives: Investigate the activity of rhythmic masseter muscles activity (RMMA) during sleep in patients with dentofacial deformities. Materials and methods: Fifty patients with dentofacial deformities (16 male, 34 female) who required orthognathic surgery. An electrode was attached to the masseter muscle bilaterally, and preoperative polysomnography was performed. The frequency of RMMA onset per hour was measured on the left and the right sides. Values were classified as phasic (grinding: P-RMMA) and tonic (clenching: T-RMMA) to examine the onset of RMMA. Correlation between the RMMA index and various morphological and physical factors were determined including sleep or awake, rapid eye movement (REM), non-rapid eye movement (NREM) phases (NR1-NR4) in the sleep stage, phasic and tonic, gender, and mandibular asymmetry. Results: The RMMA index values at the time of sleep were significantly small than during awake. The values were significantly higher during the NREM sleep than during the REM sleep and were the highest in the NR1 phase. P-RMMA index was significantly higher than the T-RMMA index. The P-RMMA index was also significantly higher than the T-RMMA index for men. In patients with greater asymmetry in the RMMA index values between the left and the right side (more than 30% difference), deviation between the midpoint of the maxillary and the mandibular incisal edges (U1-L1 deviation) was significantly higher. Conclusion: RMMA in patients with dentofacial deformity was statistically higher in awake than sleep, higher in NREM sleep than REM sleep, higher in male than female on grinding, and higher in upper and lower incisor high deviation.

Reconstruction of a defect on the buccal mucosa and prolabium.

We describe the procedure for reconstruction of a defect on the buccal mucosa and the prolabium with a buccal mucosal transposition flap and an artificial dermis graft. The preparation of the flap started with an incision extending from the border of the defect to the corner of the mouth. The pivot point of the flap was near the stump of the excised prolabium. Only the buccal mucosa was elevated from the buccal surface. It was transposed onto the defect of the prolabium and sutured to the edges of the defect. After reconstruction of the prolabium, the artificial dermis was trimmed and sutured to the mucosal and skin edges of the surgical defect. This is an easy and minimally invasive procedure to cover a defect of the buccal mucosa and the prolabium. In our experience, the wound healed with good, functional, and cosmetic results.

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

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.

Comparison of Postoperative Stability Between BSSRO and Le Fort 1 Osteotomy with BSSRO in Skeletal Class III Malocclusion with Severe Open Bite.

INTRODUCTION: We aimed to investigate postoperative stability after orthognathic surgery in patients with skeletal class III malocclusion with severe open bite by comparison between bilateral sagittal splitting osteotomy (BSSRO) and BSSRO with Le Fort 1 osteotomy. MATERIALS AND METHODS: Seventeen patients with skeletal class III malocclusion with severe open bite who were needed more than 6 degree counterclockwise rotation of distal segment by only BSSRO in preoperative cephalometric prediction. The subjects were divided into group A, where 9 patients were treated by BSSRO, and group B, where 8 patients were treated by BSSRO with Le Fort 1 osteotomy. Patient's characteristics of age, gender, preoperative over jet (OJ) and over bite (OB) were not found to be significantly different between the two groups. Counterclockwise rotation of distal segment in preoperative cephalometric prediction by only BSSRO was not found to be significantly different between group A of 7.6 (6-10.6) degree and group B of 9 (6-13) degree. The amount of rotation was reduced to 5.4 (3-10) degree by bimaxillary surgery using BSSRO and Le Fort 1 osteotomy in group B. OJ and OB were measured as occlusal stability factor. Distance between ANS-to-PNS plane and the edge of upper incisor (NF-U1Ed), and distance between Menton and edge of lower incisor (Me-L1Ed) were measured as skeletal stability factor using cephalometric analysis. These lengths were measured at pre-surgery (T0), 2 weeks after surgery (T1) and 1 year after surgery (T2), and these differences between the two groups were statistically analyzed. RESULTS: OJ and OB kept a good relation at any experimental periods. The change of Me-L1Ed was significantly larger in group A (1.21 mm at T0-T1, 1.02 mm at T0-T2) than in group B (0.14 mm at T0-T1, 0.16 mm at T0-T2). The change of NF-U1Ed was not significantly different between group A (1.07 mm at T0-T1, 0.57 mm at T0-T2) and group B (0.51 mm at T0-T1, - 0.05 mm at T0-T2). CONCLUSION: In case with more than 6 degree counterclockwise rotation of distal segment, skeletal stability was better after bimaxillary surgery than only BSSRO; however, OJ and OB kept a good relation.

Oral tumor resection and salivary duct relocation with an ultrasonic surgical aspirator.

We describe a procedure of oral tumor resection and salivary duct relocation with an ultrasonic surgical aspirator. After mucosal incision, resection of the underlying musculature was performed using an ultrasonic surgical aspirator. Using the apparatus, the salivary duct was easily exposed without damaging or cutting the duct. After identification of the salivary duct, salivary duct relocation was performed. After resection of the tumor, the artificial dermis was trimmed and sutured to the mucosal edges of the surgical defect. This method is a reliable and simple procedure that can be used to avoid postoperative complications such as salivary fistula or swelling of the gland.

Mandibular coronoid hyperplasia: a case report.

A case of unilateral coronoid hyperplasia successfully treated by coronoidotomy with prolonged postoperative physiotherapy and reveal the postoperative radiographic changes between the sectioned part of the coronoid process and the mandibular ascending ramus is described. The patient was a 28-year-old man whose maximum mouth opening was 30 mm. A coronoidotomy of the left coronoid process was performed. Nine days after surgery, the patient started physiotherapy with a HU-OS(r) appliance. After coronoidotomy and physiotherapy, the maximum mouth opening had increased to 43 mm. Radiographic follow-up showed that the coronoid process apparently united with the mandibular ascending ramus, with moderate dislocation and inclination posteriorly. In the case presented, an intraoral coronoidotomy with postoperative physiotherapy for treatment of coronoid process hyperplasia allowed satisfactory and stable results in the correction of coronoid-malar interference.

Factors related to patients' nutritional state after orthognathic surgery.

PURPOSE: The purpose of this study was to evaluate patients' nutritional state after orthognathic surgery. METHODS: The subjects were 40 female patients with dentofacial deformity aged 17-33 years who were undergoing bilateral sagittal splitting ramus osteotomy. Twenty patients were treated with intermaxillary fixation, and 20 patients were treated without intermaxillary fixation. Age and body mass index (kg/m2) were assessed as physical factors, operation time, blood loss, and amount of mandibular movement with or without intermaxillary fixation were assessed as operation stress factors, and the following laboratory data, total protein, serum albumin, total cholesterol, total lymphocytes, and cholinesterase were assessed as nutritional state factors at 1 and 2 weeks after surgery. Statistical analysis was performed for body weight loss and relationship between body weight loss and examination factors. RESULTS: Body weight significantly decreased 2.3% at 1 week and 3.9% at 2 weeks after surgery rather than preoperation. All laboratory data except total lymphocyte were decreased at 1 week after surgery and still remained significantly decreased at 2 weeks after surgery. There was a statistically significant relationship between body weight loss at 1 week after surgery and operation time. CONCLUSIONS: These results indicate that long operation time caused body weight loss in orthognathic surgery.

Three minimally invasive procedures for removing lesions in the maxillary sinus.

We describe here 3 minimally invasive procedures for removing lesions from the maxillary sinus using an ultrathin endoscope, microscope, and otoscope.Preoperatively, a lesion in the maxillary sinus was identified by radiographic examination. Then the access hole position and advance direction of the endoscope and forceps were planned. Under local anesthesia, a small incision on the buccal mucosa was made in the planned position. The anterior bony wall of the sinus was exposed subperiosteally, and a small access hole for the insertion of an endoscope was made in the planned position and angled with a fissure bur. After identification of the lesion endoscopically, microscopically, or otoscopically, a forceps was inserted into the sinus cavity through the hole, and the lesion was seized and withdrawn from the sinus.The surgical procedures are suggested to be reliable, easy, and minimally invasive that provide a limited incision and bone removal and respect the integrity of the sinus.

Tooth loss-related dietary patterns and cognitive impairment in an elderly Japanese population: The Nakajima study.

Although several studies have demonstrated a potential correlation of dietary patterns with cognitive function, the relationship between tooth loss and dietary patterns and cognitive function have not been identified. In this cross-sectional study, we used a reduced rank regression (RRR) analysis, a technique used previously to observe dietary patterns based on the intakes of nutrients or levels of biomarkers associated with the condition of interest, to identify tooth loss-related dietary patterns and investigate the associations of such patterns with cognitive impairment in 334 community-dwelling Japanese subjects aged ≥ 60 years. According to Pearson correlation coefficients, the intakes of six nutrients (ash content, sodium, zinc, vitamin B1, α- and ß-carotene) correlated significantly with the number of remaining teeth. Using RRR analysis, we extracted four dietary patterns in our subject population that explained 86.67% of the total variation in the intakes of these six nutrients. Particularly, dietary pattern 1 (DP1) accounted for 52.2% of the total variation. Food groups with factor loadings of ≥ 0.2 included pickled green leafy vegetables, lettuce/cabbage, green leaves vegetables, cabbage, carrots/squash; by contrast, rice had a factor loading of <-0.2. In a multivariate regression analysis, the adjusted odds ratios regarding the prevalence of cognitive impairment for the lowest, middle and highest tertiles of the DP1 score were 1.00 (reference), 1.224 (95% confidence interval [CI]: 0.611-2.453) and 0.427 (95% CI: 0.191-0.954), respectively. To our knowledge, this is the first report to show that tooth loss-related dietary patterns are associated with a high prevalence of cognitive impairment. These results may motivate changes in dental treatment and the dietary behaviours and thereby lower the risk of cognitive impairment.

Elastin­derived peptides are involved in the processes of human temporomandibular disorder by inducing inflammatory responses in synovial cells.

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. Fibroblast­like 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 elastin­derived peptides (EDPs) in human temporomandibular disorders. Therefore, interleukin­6 (IL­6) 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 IL­6 expression. In vitro, EDPs act on human TMJ synovial cells to promote upregulation of IL­6 and the elastin­degrading enzyme matrix metalloproteinase­12 (MMP­12). The upregulation of IL­6 and MMP­12 expression by EDPs may be mediated through elastin­binding 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 pro­inflammatory cascade and increase expression of MMP­12 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 IL­6 in the synovial fluid of the TMJ may be indicators of the pathological conditions of the joint.

Loss of epidermal growth factor receptor expression in oral squamous cell carcinoma is associated with invasiveness and epithelial-mesenchymal transition.

Inhibition of epidermal growth factor receptor (EGFR) signaling has emerged as a novel therapeutic strategy for the treatment of oral squamous cell carcinoma (OSCC). The EGFR-directed inhibitor cetuximab is currently the only approved targeted therapy for the treatment of OSCC. EGFR status may affect the patient response to cetuximab treatment. In the present study, via analysis of the immunomarker for EGFR, it was revealed that 58.3% of the total cases investigated stained positively for EGFR expression, and furthermore, that invasiveness was inversely correlated with EGFR expression. Expression levels of EGFR were quantified, and the correlation between EGFR expression and cetuximab sensitivity was investigated using three varying grades of invasive human OSCC line. EGFR expression in high-grade invasive cells was significantly downregulated compared with that of low-grade invasive cells. There was no significant antiproliferative effect in the high-grade invasive cells treated with various concentrations of cetuximab. The EMT-associated genes, N-cadherin, vimentin and Snail, were upregulated in the high-grade invasive cells. The low-grade invasive cells exhibited characteristics of typical epithelial cells, including the expression of E-cadherin and absence of the expression of N-cadherin, vimentin and Snail. Transforming growth factor-ß induced low-grade invasive cells to undergo an epithelial-mesenchymal transition (EMT)-associated gene switch, which resulted in low levels of EGFR expression. The results of the present study suggested that loss of EGFR expression in OSCC was associated with EMT, and may have functional implications with regard to tumor invasiveness and the resistance to cetuximab treatment.