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.     

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).     

Relationship of calcitonin gene-related peptide in synovial tissues and temporomandibular joint pain in humans

OBJECTIVE: To elucidate the expression of calcitonin gene-related peptide (CGRP) in synovial tissue taken from the human temporomandibular joint (TMJ) with internal derangement, and discuss the relationship between CGRP and joint pain. STUDY DESIGN: Using an immunohistochemical technique, 48 joints in 48 patients were examined. As controls, synovial tissue specimens from 7 joints with habitual dislocation without pain were also examined. RESULTS: In all of the internal derangement and control subjects, CGRP-positive cells were observed in the connective tissues around the blood vessels beneath the lining cells. The extent score of CGRP was significantly higher in the internal derangement group than in the control group (P=.033). There was a significant positive correlation between the extent score of CGRP and joint pain (P=.036, r=0.30). CONCLUSIONS: These results suggest that the expression of CGRP is increased in the synovial tissues from patients with internal derangement, and that CGRP seems to play an important role in the mechanism of pain production in patients with symptomatic internal derangement.     

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.     

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.     

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.     

Bone marrow edema of the mandibular condyle related to internal derangement, osteoarthrosis, and joint effusion.

PURPOSE: The purpose of this prospective study was to evaluate whether common magnetic resonance imaging (MRI) variables such as temporomandibular joint (TMJ) internal derangement, osteoarthrosis, and effusion may predict the diagnostic group of bone marrow edema of the mandibular condyle. MATERIALS AND METHODS: The relationship between bone marrow edema and TMJ disc displacement, osteoarthrosis, and effusion was analyzed in MRIs of 120 TMJs in 73 consecutive patients with TMJ pain and/or a clinical diagnosis of TMJ internal derangement type III (disc displacement without reduction). The diagnostic bone marrow edema group was comprised of 54 TMJs in 40 patients with a unilateral or bilateral MRI diagnosis of bone marrow edema. The control group consisted of 66 non-bone marrow edema TMJs in 33 patients with a bilateral MRI finding of an absence of bone marrow edema. A logistic regression analysis was used to compute the odds ratios for internal derangement, osteoarthrosis, and effusion for non-bone marrow edema TMJs (n = 66) versus TMJs with bone marrow edema (n = 54). RESULTS: Using Chi;(2) analysis for pair-wise comparison, the TMJ-related data showed a significant relationship between the MR imaging findings of TMJ bone marrow edema and those of internal derangement (P = .000), osteoarthrosis (P = .000), and effusion (P = .010). Of the MRI variables considered simultaneously in the multiple logistic regression analysis, osteoarthrosis (P = .107) and effusion (P = .102) dropped out as nonsignificant in the diagnostic bone marrow edema group when compared with the control group. The odds ratio for individuals with an internal derangement showing bone marrow edema was strong (3.6:1) and highly significant (P = .000). Significant increases in risk of bone marrow edema occurred with disc displacement without reduction and osteoarthrosis (9.2:1) (P = .000) and disc displacement without reduction and effusion (6.4:1) (P = .002). CONCLUSIONS: The results suggest that the MR imaging findings for TMJ bone marrow edema are related to those of internal derangement, osteoarthrosis, and effusion. However, the data re-emphasize the aspect that internal derangement, osteoarthrosis, and effusion may not be regarded as the unique and dominant factors in defining TMJ bone marrow edema instances.     

关节液蛋白含量与颞下颌关节疼痛患者影像学特征的对照研究

目的　探讨关节液中的蛋白浓度与关节影像学特征性表现及疼痛的关系。方法　采用磁共振成像 (MRI)金标准对4 0例单侧颞下颌关节 (TMJ)疼痛患者进行结构紊乱、骨关节炎及关节渗液的诊断 ,并在关节上腔冲洗治疗时收集关节液标本 ,以不存在结构紊乱、骨关节炎及关节渗液的关节液标本为对照 ,15侧无症状志愿者的关节液为正常对照 ;采用双金鸡宁酸法检测关节液中蛋白浓度。结果　患者关节液中蛋白含量的高低与结构紊乱、关节渗液及骨关节炎均无相关性 ;患者关节液中蛋白含量与正常人蛋白含量无差异。结论　关节液中的蛋白水平不能反映在影像学上代表关节炎症的结构紊乱、骨关节炎及渗出液关节的炎症状态及疼痛。     

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.     

Does joint effusion on T2 magnetic resonance images reflect synovitis? Part 3. Comparison of histologic findings of arthroscopically obtained synovium in internal derangements of the temporomandibular joint

OBJECTIVES: To evaluate the relationship between the volume of joint effusion (JE), determined by T2-weighted magnetic resonance imaging (MRI), and microscopic findings of synovial inflammation in internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: Magnetic resonance images of 53 symptomatic TMJs (53 patients) associated with painful hypomobility were taken to evaluate the degree of JE on a scale of 0 to 3. Within 2 months after MRI, biopsy specimens obtained by arthroscopy were quantitatively assessed, on the basis of Gynther's grading system, for severity of hyperplasia of synovial lining cell layers, vascularity, and the presence of inflammatory cells. Each synovitis score was compared among the 4 JE grades, as well as between 2 groups-effusion present (grades 2 and 3) and effusion absent (grades 0 and 1)-by using the Spearman correlation coefficiency and the Mann-Whitney U test. RESULTS: The distribution of JE was as follows: 14 joints had grade 0, 9 joints had grade 1, 19 joints had grade 2, and 11 joints had grade 3. Significant relationships were found between the grades of JE and scores of synovial lining cell layers (P =.0012) as well as between the grades of JE and scores of presence of inflammatory cells (P =.0064). The joints with effusion had significantly higher scores for synovial lining cell layers (2.0 +/- 0.2) than the joints without effusion (1.3 +/- 0.2) (P =.029). There was no statistically significant correlation between the scores of vascularity and JE (P =.394). CONCLUSIONS: The evidence of JE on MRI might correlate with synovial inflammatory activity. It confirms the common consensus that JE probably reflects synovitis, especially when synovial hyperplasia has a key role in the pathogenesis of JE.     

Temporomandibular joint pain: relationship to internal derangement type, osteoarthrosis, and synovial fluid mediator level of tumor necrosis factor-alpha

OBJECTIVES: The purpose of this study was to investigate whether patients with temporomandibular joint (TMJ)-related pain classified as capsulitis/synovitis may be linked to magnetic resonance imaging (MRI) findings of internal derangement, osteoarthrosis, or the synovial fluid aspirate findings of tumor necrosis factor-alpha (TNF-alpha) level. STUDY DESIGN: The study comprised 23 patients with temporomandibular disorders (TMD), who had nonchronic pain (pain onset < or =6 months) and a unilateral TMJ-related diagnosis of capsulitis/synovitis. Bilateral sagittal and coronal magnetic resonance images were obtained to establish the presence or absence of internal derangement, osteoarthrosis, or both. TMJ synovial fluid aspirates were obtained from the pain and contralateral nonpain sides to determine the TNF-alpha level. RESULTS: Comparison of the TMJ side-related data showed a significant relationship between the clinical TMD diagnosis of capsulitis/synovitis and the MRI diagnoses of TMJ internal derangement (P =.002) and of TMJ internal derangement type (P =.04). The mean TNF-alpha level in synovial fluid aspirates from TMJs assigned a clinical TMD diagnosis of capsulitis/synovitis was significantly higher than in those obtained from contralateral nonpain sides (P =.001). There was no correlation between the clinical diagnosis of capsulitis/synovitis and the MRI diagnosis of TMJ osteoarthrosis (P =.13) or between the MRI diagnosis of TMJ osteoarthrosis and that of TMJ internal derangement (P =.70) or TMJ internal derangement type (P =.33). CONCLUSIONS: The results suggest that the TMJ pain condition of capsulitis/synovitis is related to TMJ-side specific MRI diagnoses of internal derangement and internal derangement type, and synovial fluid aspirate findings of TNF-alpha level. The data confirm the concept of elevated mediator level as a diagnostic approach for patients presenting with TMJ-related pain. MRI and synovial fluid aspirates may be used as diagnostic methods for evaluating TMJ-related pain conditions.     

Comparison of cytokine level in synovial fluid between successful and unsuccessful cases in arthrocentesis of the temporomandibular joint.

PURPOSE: The aim of this study was to compare proinflammatory cytokine levels between successful cases and unsuccessful cases of arthrocentesis in patients with internal derangement of the temporomandibular joint (TMJ). PATIENTS AND METHODS: This study involved 73 joints judged as successful and 30 judged as unsuccessful of 103 joints in 100 patients diagnosed with internal derangement of the TMJ and who underwent arthrocentesis. The diluted synovial fluid before undergoing arthrocentesis was aspirated from the superior joint space. The concentrations of interleukin (IL)-1beta, tumor necrosis factor-alpha, IL-6, and IL-8 were measured using an enzyme-linked immunosorbent assay. The differences in the detection rate and concentration of each cytokine between successful cases and unsuccessful cases were analyzed statistically. RESULTS: There was a statistically significant difference between successful cases (72.2%) and unsuccessful cases (95.5%) in the detection ratio of IL-6 (P <.05). There was a statistically significant difference between successful cases (0.017 pg/100 microg protein) and unsuccessful cases (0.046 pg/100 microg protein) in the concentration of IL-1beta (P <.05). CONCLUSION: It has been shown that the presence of IL-1beta and IL-6 in synovial fluid may be indicators of possible unsuccessful treatment following arthrocentesis for internal derangement of the TMJ.     

Acoustic characteristics of sounds from temporomandibular joints with and without effusion: an MRI study

Joint effusion has been associated with temporomandibular joint (TMJ) pain but can only be diagnosed by magnetic resonance imaging (MRI). For screening of patients with suspected effusion a simple and less expensive method would be desirable. We recorded joint sounds during jaw opening and closing movement from 34 TMJs with internal derangement (ID). Seventeen joints had joint effusion seen on MRI. Spectrograms of the sounds were displayed as waterfall plots showing profiles of the consecutive Hamming windows. If the profiles were similar, as judged by initial evaluation, the displayed pattern was classified as stable. If some profiles were distinctly deviating in their pattern, this was classified as unstable. Joints with effusion showed unstable sound pattern more often than joints without effusion (P < 0.001). It was concluded that TMJ sound analyses have a potential to identify joints with effusion based on their unstable sound pattern.     

Importance of the changes in joint effusion shown by magnetic resonance imaging before and after arthroscopic lysis and lavage of the temporomandibular joint

We investigated the changes in the amount of joint effusion estimated from T2-weighted magnetic resonance imaging (MRI) before and after arthroscopic lysis and lavage of the temporomandibular joint (TMJ). We studied 29 consecutive patients, each with internal derangement and osteoarthritis in one TMJ. Before operation, the MRI showed joint effusions in 22 of the patients (76%). After operation, the amount of the effusion decreased in 16 and increased in 2 patients. Effusions developed postoperatively in four of the seven patients who had no effusion before operation. In four of the six patients in whom the effusion increased, the symptoms had almost resolved by the time the MRI was taken. There was no significant correlation between changes in the amount of joint effusion and the clinical condition of the patients before and after the operation. In conclusion, changes in the amount of joint effusion in the TMJ are not related to the patient's clinical condition.     

Risk factors for temporomandibular joint pain in patients with disc displacement without reduction - a magnetic resonance imaging study

The purpose of this study was to evaluate whether the magnetic resonance (MR) imaging variables of temporomandibular joint (TMJ) internal derangement, osteoarthrosis and/or effusion may predict the presence of pain in patients with a clinical disorder of an internal derangement type (ID)-III. The relationship between TMJ ID-III pain and TMJ internal derangement, osteoarthrosis and effusion was analysed in MR images of 84 TMJs in 42 patients with a clinical unilateral diagnosis of TMJ ID-III pain. Criteria for including a TMJ ID-III pain patient were report of orofacial pain referred to the TMJ, with the presence of unilateral TMJ pain during palpation, function and/or unassisted or assisted mandibular opening. Bilateral sagittal and coronal MR images were obtained to establish the presence or absence of TMJ internal derangement, osteoarthrosis and effusion. Using chi-square analysis for pair-wise comparison, the data showed a significant relationship between the MR imaging findings of TMJ ID-III pain and those of internal derangement (P=0.01) and effusion (P=0.00). Of the MR imaging variables considered simultaneously in the multiple logistic regression analysis, osteoarthrosis (P=0.82) and effusion (P=0.08) dropped out as non-significant in the diagnostic TMJ pain group when compared with the TMJ non-pain group. The odds ratio that a TMJ with an internal derangement type of disk displacement without reduction might belong to the pain group was strong (2.7:1) and highly significant (P=0.00). Significant increases in risk of TMJ pain occurred with 'disk displacement without reduction in combination with osteoarthrosis' (5.2:1) (P=0.00) and/or 'disk displacement without reduction in combination with osteoarthrosis and effusion' (6.6:1) (P=0.00). The results suggest that TMJ pain is related to internal derangement, osteoarthrosis and effusion. However, the data re-emphasize the aspect that these MR imaging variables may not be regarded as the unique and dominant factors in defining TMJ pain instances.     

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.     

Inflammatory change in the upper joint space in temporomandibular joint with internal derangement on gadolinium-enhanced MR imaging

The object of this study was to clarify the relationship between gadopentetate dimeglumine (Gd-DTPA) contrast enhancement of the upper joint space and the severity of internal derangement of the temporomandibular joint (TMJ). Fifty patients with 63 painful TMJs underwent 1.5T MR imaging with T1-weighted images before and after an intravenous injection of Gd-DTPA with or without fat suppression. The relationship was investigated between the contrast enhancement at the upper joint space and disc position, disc morphology or bone morphology. Of the 63 joints, a significant contrast enhancement in the upper joint space was detected in 32 joints. There was a significant high incidence of anterior disc displacement without reduction in the contrast-enhancement positive group compared to the negative group (P = 0.021), but there was no significant difference for disc morphology (P = 0.094) and bone morphology (P = 0.384). Gd-DTPA enhanced MR imaging may potentially have diagnostic value for internal derangements of TMJs.     

颞下颌关节渗出液与内紊乱的关系

目的探讨渗出液与颞下颌关节内紊乱(TMJID)的关系,揭示渗出液的成因。方法用磁共振成像技术,对44例单侧关节疼痛、颞下颌关节紊乱病患者88侧关节完成开闭口T1、闭口T2加权成像,观察TMJID与关节腔渗出液的发生率。结果33个关节腔存在渗出液,占37.5%,其中21个(63.6%)表现为TMJID:9个(27.3%)为可复性关节盘前移位(ADDR),12个(36.3%)为不可复性关节盘前移位(ADDWR);而55个无渗出液的关节中,15个(27.3%)表现为TMJID,其中8个(14.5%)为ADDR,7个(12.8%)为ADDWR。经统计学分析,TMJID的发生在有渗出液关节与无渗出液关节差异具有统计学意义(P<0.05);去除少量渗出液的关节后,进一步分析发现两者差异仍有统计学意义(P<0.05)。结论渗出液可能反映了盘突关系异常所致的关节内炎症反应的存在。     

Proinflammatory cytokines and arthroscopic findings of patients with internal derangement and osteoarthritis of the temporomandibular joint

This study investigated the correlations between the concentrations of proinflammatory cytokines in synovial fluid and the degree of synovitis on the one hand, and the degree of degeneration of articular cartilage on the other hand, in patients with internal derangement and osteoarthritis of the temporomandibular joint. We measured the concentrations of interleukin-1beta (IL-1beta), tumour necrosis factor-alpha (TNF-alpha), IL-6 and IL-8 in synovial fluid and the degree of arthroscopic synovitis and degeneration of articular cartilage in 37 joints with internal derangement and osteoarthritis. The correlations between the concentration of each cytokine and the score of each arthroscopic feature were analysed statistically. The detection rates of IL-1beta,TNF-alpha, IL-6 and IL-8 were 57%, 78%, 89% and 70%, respectively. There was a positive correlation between the IL-6 concentration and the synovitis score (P = 0.02). Measurement of IL-6 in synovial fluid might be useful as an indicator of the extent of synovitis.     

A prospective evaluation of the effectiveness of temporomandibular joint arthroscopy

This is a prospective study to evaluate therapeutic arthroscopy for internal derangement of the temporomandibular joint (TMJ). Fifty-nine patients with 76 abnormal joints were evaluated preoperatively for pain, noise, maximal incisal opening (MIO), and deviation on opening. Preoperative and postoperative magnetic resonance imaging (MRI) scans were obtained for 29 joints. Patients were treated by superior joint arthroscopy, lysis of adhesions, lavage, and steroid injection, along with preoperative and postoperative splint and physiotherapy. Pain, noise, and motion were evaluated at three time periods: 1) early (10 to 30 days); 2) intermediate (1 to 6 months); and 3) late (greater than 6 months). At early, intermediate, and late follow-up, increase in MIO was statistically significant (P less than .05). Noise did not return in the majority of patients. Disc position, evaluated by MRI, did not appear to change in 25 of 29 joints and did not correlate with clinical outcome. The results of this study indicate that TMJ arthroscopy is effective in reducing pain and increasing motion in patients with TMJ internal derangement.