Superoxide dismutase activity in synovial fluids in patients with temporomandibular joint internal derangement.

PURPOSE: To measure the activity of superoxide dismutase (SOD) in the synovial fluid of patients with temporomandibular joint internal derangement and to show the relationship between the activity of SOD and the severity of the disease. MATERIALS AND METHODS: Twenty patients with internal derangement were classified according to Wilkes by clinical radiological examinations. SOD activity was measured by the method based on nitrobluetetrazolium reduction rate. RESULTS: The activity of SOD seemed to be progressively decreased as the stage of the disease increased. CONCLUSION: The reduction of SOD activity observed may result from insufficient scavenging capacity of free radicals. Further investigation and longitudinal studies are required to determine the role of antioxidants that scavenge the free radicals in temporomandibular joint disorders.     

The expression of vascular endothelial growth factor in synovial tissues in patients with internal derangement of the temporomandibular joint

OBJECTIVE: The aim of this study was to elucidate the expression and localization of vascular endothelial growth factor (VEGF) in synovial tissue taken from the temporomandibular joint (TMJ) with internal derangement (ID) and discuss the role of VEGF in the pathogenesis of ID. STUDY DESIGN: Through the use of an immunohistochemical technique, 39 TMJs in 37 patients were examined. As controls, synovial tissue specimens from 6 joints in 6 patients with habitual dislocation were also examined. RESULTS: In the synovial tissue from 35 of the patients with ID, expression of VEGF was observed in the synovial lining cells, in the endothelial cells of the blood vessels, and in the fibroblasts. In contrast, expression of VEGF was found in the TMJ tissue from only 2 of the controls. The percentage of VEGF-positive cells in the ID specimens was significantly higher than that in the habitual dislocation specimens (P < .02), and the expression of VEGF significantly correlated with the arthroscopic synovitis score (P = .004). CONCLUSION: These results suggest that the expression of VEGF is upregulated and involved in the development of inflammatory changes in synovial tissues in TMJs with ID.     

Expression of interleukin 6 in synovial tissues in patients with internal derangement of the temporomandibular joint

Using an immunohistochemical technique, we examined synovial tissue from 46 temporomandibular joints (TMJ) with internal derangement in 44 patients. As controls, we examined synovial tissue specimens from 7 joints with habitual dislocation without pain. In synovial tissues from 21 of the 46 joints with internal derangement, interleukin 6 (IL-6) was expressed in the synovial lining cells and in the mononuclear cells infiltrating the periphery of the blood vessels. The density of IL-6-stained cells in specimens with internal derangement correlated significantly with the grade of joint effusion shown by magnetic resonance imaging (P=0.01, r=0.32).     

Vascular endothelial growth factor concentrations in synovial fluids of patients with symptomatic internal derangement of the temporomandibular joint

BACKGROUND: Vascular endothelial growth factor (VEGF) is an inducer of angiogenesis and permeability of small blood vessels. We determined the concentrations of VEGF in synovial fluid of patients with symptomatic internal derangement of the temporomandibular joint (TMJ). METHODS: Diluted synovial fluid was collected by a pumping procedure from 22 TMJs of patients with internal derangement and 10 control TMJs. VEGF concentration was determined by an enzyme-linked immunosorbent assay. RESULTS: The VEGF was detected in 14 of the 22 joints (64%) of patients with internal derangement, at a mean concentration of 67 pg/ml, but in only one control joint (12.5 pg/ml) (P = 0.004 for the difference in concentration). There was a significant correlation between VEGF concentration and total protein concentration in the synovial fluid (P = 0.002). CONCLUSIONS: The increased concentration of VEGF in patients with symptomatic internal derangement suggests that this growth factor may be involved in the pathogenesis of this condition.     

Levels of fibroblast growth factor 2 in synovial fluids in human patients with internal derangement of the temporomandibular joint

OBJECTIVE: We sought to elucidate the levels of fibroblast growth factor 2 (FGF-2) in synovial fluid taken from internally deranged human temporomandibular joints (TMJs) and to discuss the role of FGF-2 in the pathogenesis of internal derangement. STUDY DESIGN: Through the use of a pumping procedure, diluted synovial fluid was collected from the upper joint compartment of 22 TMJs with evidence of internal derangement (21 patients) and 8 TMJs with no such evidence (5 control subjects). Two of the control subjects were patients who had habitual dislocation, and three were healthy volunteers. The level of FGF-2 in the synovial fluid was assessed by means of an enzyme-linked immunosorbent assay. RESULTS: FGF-2 levels were at detectable levels in 15 of the 22 TMJs (68%) with internal derangement. The mean concentration of FGF-2 was 24 pg/mL. In the control group, FGF-2 levels were detectable in only 1 of 8 joints (13%), for a concentration of 3 pg/mL. The mean concentration of FGF-2 in the synovial fluid was significantly higher in the internal derangement group than in the control group (P =.02). CONCLUSIONS: FGF-2 levels are elevated in the human synovial fluid of TMJs with internal derangement.     

Microbiological investigation of retrodiscal tissues from patients with advanced internal derangement of the temporomandibular joint

The aim of this study was to investigate the presence of bacteria in samples of retrodiscal tissues taken from patients suffering from advanced internal derangement of the temporomandibular joint (TMJ). 12 fresh retrodiscal tissue samples were taken from 12 consecutive patients who underwent unilateral TMJ discectomy for advanced TMJ internal derangement (Wilkes stage IV). The retrodiscal tissue samples were stained and cultured for the presence of micro-organisms in microbiology laboratories. No evidence of bacteria or other micro-organisms was found in any of the tissue specimens procured from the TMJ. This study failed to identify the presence of bacteria or other micro-organisms in fresh retrodiscal tissue specimens of the TMJ in patients with advanced TMJ internal derangement.     

Immunohistochemical localization of cyclooxygenase-1 and -2 in synovial tissues from patients with internal derangement or osteoarthritis of the temporomandibular joint

This study examined the immunohistochemical expression and localization of cyclooxygenase-1 and -2 (COX-1 and COX-2) in synovial tissues from patients with internal derangement (ID) or osteoarthritis (OA) of the temporomandibular joint (TMJ). Synovial tissues from patients with condylar fractures of the mandible were studied as control. Synovial tissues from 13 TMJs of 10 patients with ID or OA and from 5 TMJs of 4 patients with fractures were examined for COX-1 and COX-2 expression by immunohistochemical staining using two monoclonal antibodies. In addition, whether the COX-2 expression grade correlated with the synovitis score and clinical findings was assessed. COX-2 was expressed in the synovial lining, infiltrating mononuclear cells, fibroblast-like cells, and blood vessels, including CD31-positive endothelial cells, in the synovium of patients with ID or OA. Expression levels of COX-1 in synovial lining cells and endothelial cells were similar in the specimens obtained from the patients with ID or OA and those obtained from the controls. The expression of COX-2 positively correlated with arthroscopic findings of synovitis (p = 0.55, P = 0.023) and with joint pain (p = 0.56, P = 0.021). These results suggest that up-regulation of COX-2 in synovium may play a part in the pathogenesis of synovitis in patients with ID or OA of the TMJ.     

TMJ结构紊乱患者关节液纤维蛋白含量的测定及意义

目的:测定颞下颌关节(temporomandibular joint,TMJ)结构紊乱(internal derangement,ID)患者关节液中纤维蛋白的含量,并探讨其意义.方法:选取2007年12月—2008年6月期间收治的TMJ疾病患者进行临床检查,在初步诊断为结构紊乱后进行MRI检查,以获取评价关节盘情况的影像学依据,并按照Wilkes-Bronstein分期标准进行分期,将处于Ⅱ～Ⅴ期的患者纳入治疗范围,进行关节镜下盘复位固定手术,在关节镜手术前采集关节液1m L,-40℃或-70℃冰箱低温保存.采用免疫荧光激光共聚焦显微镜半定量测定纤维蛋白的含量.按照ID分期、不同年龄段、男女分组及左右侧关节分组,应用SPSS 16.0软件包对所得数据进行t检验,比较不同组别之间关节液的平均荧光强度的差异.结果:所有125侧关节液的免疫荧光强度平均为4.43±3.67(0～31.68).ID各期关节液的平均荧光强度Ⅱ期为2.38±1.17,Ⅲ期为4.68±3.98,Ⅳ期为4.80±2.80,Ⅴ期为3.58±2.64,其中Ⅱ期与Ⅲ期(P=0.0065＜0.05)、Ⅳ期(P=0.0207＜0.05)之间有显著差异.男性患者关节液的荧光强度平均为4.05±2.70,女性患者关节液的荧光强度平均为5.57±4.71,男女之间有显著差异(P＜0.05).左侧TMJ关节液的平均荧光强度为4.37+3.04,右侧平均为5.97±5.20,两者有显著差异(P＜0.05).10～19岁为4.55±2.45,20～29岁为4.56±3.39,30～39岁为2.60±1.12,40岁以上为5.68±6.71,其中第1和第3组,第2和第3组及第3和第4组年龄段之间有显著差异.结论:关节液的平均荧光强度随着ID分期增高,呈现升高趋势,为IA形成假说提供了理论支持.     

Specific expression of substance P in synovial tissues of patients with symptomatic, non-reducing internal derangement of the temporomandibular joint: comparison with clinical findings

Our aim was to find out the extent of expression of substance P in synovial tissue from the human temporomandibular joints (TMJ) with symptomatic, non-reducing internal derangement, and to investigate the relationship between substance P and clinical findings. Fifty-four joints in 54 patients were examined immunohistochemically. Specimens of synovial tissue from 10 joints in 8 subjects with habitual dislocation of the TMJ with no pain were examined as controls. Cells that stained for substance P were found mainly among the endothelial cells in the blood vessels beneath the lining cells in synovial tissues from 47 of the 54 joints (87%) with internal derangement and from 5 of the 10 control joints. The extent score of cells that stained for substance P in joints with internal derangement was significantly higher than that in controls (p=0.02). The extent score of these cells did not correlate with pain in the joint or the degree of synovitis. These results suggest that substance P may have some roles in both the physiological and pathological conditions in patients with symptomatic internal derangement of the TMJ.     

Correlation between the arthroscopic diagnosis of synovitis and microvessel density in synovial tissues in patients with internal derangement of the temporomandibular joint.

OBJECTIVE: To elucidate the correlation between the arthroscopic diagnosis of synovitis and microvessel density in synovial tissues in patients with internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: Forty-three joints in 41 patients with internal derangement were examined and biopsies taken. Microvessel density was evaluated using the immunohistochemical method for CD 34 antibody. Arthroscopically diagnosed synovitis was evaluated according to Murakami's criteria. RESULTS: In patients with internal derangement, arthroscopically diagnosed synovitis scores averaged 5.2+/-2.0, according to Murakami et al. (1991). Small to large blood vessels were observed clearly with CD 34 stain. The mean microvessel density was 22.7+/-15.6 per two high power fields (magnification x200). Synovitis scores correlated significantly with microvessel density (p=0.002, r=0.43). CONCLUSION: Synovitis evaluated using Murakami's scores correlated well with the number of blood vessels in synovial tissues in patients with internal derangement of the TMJ. This demonstrates that synovitis is linked to inflammation-related blood vessel density of the synovial tissues.     

Matrix metalloproteinases in mild and severe temporomandibular joint internal derangement synovial fluid

OBJECTIVES: The first objective of this study was to verify the presence of and identify the molecular forms of matrix metalloproteinases (MMPs), including collagenases (MMP-1, MMP-8, and MMP-13) and gelatinases (MMP-2 and MMP-9), in the synovial fluid (SF) of mild and severe temporomandibular joint internal derangement (TMJ-ID). Another objective was to evaluate whether the SF MMPs are potential diagnostic markers that reflect the stage of intra-articular inflammation in the TMJ. STUDY DESIGN: The subjects were 44 patients with mild (n = 16) or severe (n = 28) TMJ-ID; they were classified on the basis of subjective symptoms, clinical and radiographic findings, and surgical observations. The patients were surgically treated, and SF samples were collected immediately before the operation. The collagenase activity of SF samples was analyzed by means of a type I collagen degradation assay. The levels and molecular forms of the SF MMPs as well as the tissue inhibitors of MMPs (TIMP-1 and TIMP-2) were analyzed with Western immunoblotting and gelatin zymography. RESULTS: The SF of both the mild and the severe TMJ-ID patients exhibited free collagenase activity and activity capable of further degrading the (3/4)(alphaA) fragments. Ninety-two-kilodalton proMMP-9 and its 121-kD complex form, as well as 72-kD proMMP-2 were significantly increased in the mild TMJ-ID group (P <.05 in all cases). Both 70- to 80-kD neutrophil type and 45- to 55-kD mesenchymal cell-type MMP-8 (corresponding to the latent and active forms) were observed in mild and severe TMJ-ID SF, but they predominated in mild TMJ-ID. Both MMP-1 and MMP-13 were observed in both groups, and in mild TMJ-ID SF the low-molecular weight forms of MMP-1 indicated activation of the enzyme. CONCLUSIONS: The degradation of type I collagen in the TMJ is evidently due to the collective action of many collagenolytic MMPs present in the SF of patients with mild and severe TMJ-ID. The elevated levels of MMP-2, MMP-9, and MMP-8 in the SF of patients with mild TMJ-ID eventually reflect the active phase of TMJ destruction. These observations may have considerable diagnostic and therapeutic significance in the management of TMJ disorders.     

Lubricin immunohistochemical expression in human temporomandibular joint disc with internal derangement

J Oral Pathol Med (2011) 40 : 587–592 Lubricin is a chondroprotective, mucinous glycoprotein which contribute to joint lubrication, especially to boundary lubrication and maintains joint integrity. The present investigation aimed to study the immunolocalization of lubricin in TMJ discs from patients affected by anterior disc displacement with reduction (ADDwR) ADDwoR. Eighteen TMJ displaced disc affected by ADDwoR were processed immunohistochemically, with a polyclonal anti‐lubricin antibody, used at 1:50 working dilution. The percentage of lubricin immunopositive cells (extent score = ES) and the extent of lubricin staining of the disc extracellular matrix (ECM), were evaluated. Each sample was scored for histopathological changes. Percentage of immunostained surface disc cells was the same (ES = 4) in both control and ADDwOR cells, being this data not statistically significant (P < 0.05). In pathological specimens the percentages of lubricin‐stained cells was very high with an ES of 4 respect to control specimen, and this difference was statistically significant different (P > 0.05). The extracellular matrix (ECM) of discs at the disc surfaces of both pathological and normal specimens was very heavily stained (++++). Both the ES and ECM staining were not statistically correlated to the TMJ degeneration score according to the Spearman’s rank correlation coefficient. According to our findings, a longstanding TMJ disc injury, affects lubricin expression in the TMJ disc tissue and not its surfaces, moreover, lubricin immunostaining is not correlated to TMJ disc histopathological changes.     

Bite-force endurance in patients with temporomandibular joint osteoarthrosis and internal derangement

The aim of this study was to investigate the potential clinical relevance of testing bite force endurance in patients with articular temporomandibular disorders. The endurance of a 50 N bite force was measured in 51 patients with painful temporomandibular joint disorders. The results were compared to those of a control group of 20 subjects. The force exerted was sustained until this task could not be continued because of intolerable pain or fatigue. The endurance test was repeated following therapy. Testing bite force endurance could be reliably carried out (paired t-test not significant, product-moment correlation coefficient 0.87). The mean endurance time in the patient group was significantly different from that of the control group (t = 7.43, df = 69, P < 0.01). The 95% confidence intervals for patients and controls did not show any overlap. No difference in endurance time between diagnostic subgroups could be detected (F = 1.30, df = 4,46, P < 0.28). Following treatment, all patients showed a significant increase of endurance time (t = 8.09, df = 50, P < 0.01) and reported a decrease in post-test pain. The mean difference between pre- and post-treatment endurance was 60s. Subjects of the control group stopped the biting effort predominantly because of muscle fatigue. By contrast, the main reason of the patients to cease the effort was TMJ pain. The results of this study indicate that the discriminatory power of the test is sufficient to justify its utility as a complementary tool in assessing the functional capacity of the masticatory system.     

Relation between the expression of vascular endothelial growth factor in synovial tissues and the extent of joint effusion seen on magnetic resonance imaging in patients with internal derangement of the temporomandibular joint

The aim of this study is to elucidate the relation between the expression of vascular endothelial growth factor (VEGF) in synovial tissues and the extent of joint effusion seen on magnetic resonance imaging (MRI) in patients with internal derangement of the temporomandibular joint (TMJ). Using an immunohistochemical technique, we examined specimens of synovial tissues from 41 joints in 40 patients with internal derangement. Specimens from 36 of the 41 joints stained for VEGF. There was a significant correlation between the percentage of the VEGF-stained cells and the grade of joint effusion seen on MRI (P=0.0002, r=0.62). The correlation between the two was also significant on multiple logistic regression analysis (P=0.003, odds ratio=1.75). These results suggest that VEGF may have an important role in the genesis of joint effusion.     

Correlations of the expression of fibroblast growth factor-2, vascular endothelial growth factor,and their receptors with angiogenesis in synovial tissues from patients with internal derangement of the temporomandibular joint

Synovitis in internal derangement of the temporomandibular joint (TMJ) is accompanied by the growth of new blood vessels. Fibroblast growth factor-2 (FGF-2) and vascular endothelial growth factor (VEGF) are well-characterized angiogenic factors. The objective of this study was to elucidate the correlation between the expression of FGF-2, VEGF, and their receptors-FGF receptor-1 (FGFR-1) and VEGF receptor-1 (Flt-1)-with microvessel density in synovial tissues of the TMJ. Using an immunohistochemical technique, we examined 47 joints (45 patients) with internal derangement. Individual microvessel density was evaluated by means of the CD34 antibody, a specific endothelial marker. The correlation between the percentage of immuno-positive cells and microvessel density was evaluated. In multiple logistic regression analysis, the correlation between the percentage of Flt-1-positive cells and microvessel density was significant [p = 0.005, odds ratio = 1.071, 95% confidence interval = 1.021-1.124]. These results suggest that the expression of the VEGF/Flt-1 system is involved in angiogenesis in inflamed synovial tissue in the TMJ.     

Co-expression of interleukin-1β and tumor necrosis factor α in synovial tissues and synovial fluids of temporomandibular joint with internal derangement: comparision with histological grading of synovial inflammation

BACKGROUND: It has been clarified that interleukin-1 (IL-1)beta and tumor necrosis factor (TNF)alpha play an important role in pathogenesis of various joint disease. The purpose of this study was to investigate the cellular source of IL-1beta and TNFalpha in temporomandibular joint (TMJ), and to analyze the relation between the expression of these cytokines and the intensity of TMJ synovial inflammation. METHODS: We examined 33 synovial biopsy specimens from patients with internal derangement of the TMJ by an immunohistochemical technique using specific antibodies to IL-1beta and TNFalpha. We also studied 20 synovial fluids from the patients by enzyme-linked immunosorbent assay method. These data are compared with histological grading of synovial inflammation by Gynther's system. RESULTS: Both IL-1beta and TNFalpha were predominantly localized in the synovial lining cell layer and the blood vessels of synovial biopsy specimens obtained from patients with TMJ internal derangement. A statistically significant correlation was found between the intensity of IL-1beta expression and that of TNFalpha. Additionally, the intensity of TNFalpha expression was statistically correlated with histological grading by Gynther's system. CONCLUSION: These results supported that IL-1beta and TNFalpha may be involved in the occurrence of TMJ internal derangement and that they coordinately play an role in pathogenesis of TMJ internal derangement.     

Long-term evaluation of 211 patients with internal derangement of the temporomandibular joint

This report is a long-term evaluation of 211 patients (158 women, 53 men) with TMJ clicking and/or TMJ incoordination, treated at the University Hospital of Copenhagen, Denmark, in the years 1971-77. Information on present symptoms and the effect of the initial treatment was obtained from questionnaires. Standard treatment procedures had been used in 153 patients while 58 patients had had counseling only. In the actively treated group, 59% were still doing well, 30% had unchanged symptoms and 5% experienced aggravated symptoms. In the counseled group, 40% were free of symptoms, 50% had unchanged symptoms and 7% aggravated symptoms. A highly significant association was found between the absence or presence of symptoms at the end of treatment according to patient records and the evaluation of the initial effect of treatment 8-15 yr later, which indicates that reliable results can be expected from a long-term evaluation of TMJ dysfunction patients. In the sample as a whole, the frequency of TMJ sounds was unchanged compared to the time of treatment (64% vs 66%). A significantly higher frequency was, however, found in the untreated group, indicating that treatment might have a positive effect on TMJ sounds. The frequency of recurrent headache had increased considerably over the years (6% vs 34%), 32% still experienced pain/tenderness on mandibular movement, 24% suffered from impaired mandibular mobility and 82% were aware of bruxism/clenching of teeth. Furthermore, we found a significant association between headache before treatment and headache, awareness of bruxism and clenching of teeth at the time of evaluation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of exercise therapy in patients with internal derangement of the temporomandibular joint

This study intended in evaluating the effectiveness of exercise therapy in patients with craniomandibular disorders (CMD). Twenty consecutive patients suffering from CMD with anterior disc displacement without reduction consulting a CMD service were included in the study if they met following criteria: (i) pain in the temporomandibular region, (ii) reduced incisal edge clearance (<35 mm), (iii) magnet resonance imaging confirmed anterior disc displacement without reduction and (iv) evidence of postural dysfunction. All patients were assigned to a waiting list, serving as a no-treatment control period, according to a before-after trial. The treatment consisted of active and passive jaw movement exercises, correction of body posture and relaxation techniques. A total of 18 patients completed the study, no adverse effects occurred. Following main outcome measures were evaluated: (1) pain at rest (2) pain at stress (3) impairment (4) mouth opening at base-line, before and after treatment and at 6 month follow-up. As a result of treatment pain, impairment and mouth opening improved significantly more than during control period (paired samples t-test P < 0.05). After treatment four patients had no pain at all (chi-square: P < 0.05) and only seven patients revealed an impaired incisal edge clearance after treatment. (chi-square Test, P < 0.001). At follow up, seven patients had no pain and experienced no impairment. Exercise therapy seems to be useful in the treatment of anterior disc displacement without reduction.