The expression of transforming growth factor beta (TGF-beta) in the synovial membrane of human temporomandibular joint with internal derangement: a comparison with tenascin expression

We examined the expression of the transforming growth factor beta (TGF-beta) in 28 human temporomandibular joint (TMJ) samples (internal derangement of TMJ and control specimens) by an immunohistological method using paraffin-embedded tissues and a polyclonal antibody specific to human TGF-beta. The resulting reaction of TGF-beta expression divided into three types as follows. The first type, around the fibrocyte and in the lacunae of chondrocytes in the disc. The second type, at the stroma of the mildly hypertrophic synovial membrane and severely hypertrophic synovial membrane. The first type was observed in all the cases including the control cases. The second type showed only in the internal derangement of TMJ, and its expression pattern resembled that of tenascin (TN) within the stroma of hypertrophic synovial membranes. In conclusion, TGF-beta and TN were distributed in the affected synovial membrane of TMJ with internal derangement. These findings suggested that TGF-beta and TN might have a close relationship with synovitis, followed by tissue repair.     

The immunohistochemical distribution of vimentin in human temporomandibular joint samples

The aim of this investigation was to evaluate the immunohistochemical distribution of vimentin in the temporomandibular joint (TMJ) and to compare it with the control specimens. Immunohistochemical distribution in the disc and synovial membrane in 30 human TMJ (internal derangement of TMJ, n = 20; and control, n = 10) was studied immunohistologically using paraffin-embedded tissue and specific anti-human vimentin monoclonal antibody. Vimentin expression was distributed in chondrocyte-like cells, synovial cells and endothelial cells. There was an obvious distinction of vimentin immunoreactivity between the control specimens and internal derangement cases, in the posterior and/or anterior loose connective tissues. In particular, intensive vimentin expression was detected in the hypertrophic synovial membrane of internal derangement cases. The findings of the present study suggest that vimentin might be an important marker of pathological hypertrophy of the synovial membrane and/or connective tissue with internal derangement of TMJ.     

The expression of tenascin mRNA in human temporomandibular joint specimens

The expression of mRNA of tenascin in the temporomandibular joint (TMJ) disc and synovial membrane was examined in 20 human TMJ samples from patients with internal derangement of the TMJ and 10 control specimens by in situ hybridization technique using paraffine-embedded tissue, and antisense and sense cRNA probes. In control specimens, tenascin mRNA was not expressed. However, we were able to find tenascin mRNA expression in the surgical specimens. In 15 of 20 samples, ranging numbers of synovial cells expressed tenascin mRNA in the hypertrophic synovial membranes. Also, in 6 of 20 samples, tenascin mRNA was identified in fibroblasts. In four specimens, vascular endothelial cells were positive for the mRNA. In internal derangement cases, histopathological findings are often found such as synovitis, new capillary growth and fibrosis. The present study demonstrates that tenascin is produced specifically in synovial cells, vascular endothelial cells and fibroblasts affected in the portion of TMJ with internal derangement.     

Angiogenesis in the human temporomandibular joint studied by immunohistochemistry for CD34 antigen

The CD34 antigen is a sensitive marker of vascular endothelium and angiogenesis. Thus, we examined the expression of CD34 in 20 human temporomandibular joint (TMJ) samples with internal derangement and in 10 control specimens by an immunohistological technique using paraffin-embedded tissue and specific anti-human CD34 monoclonal antibody. In the control specimens, CD34 was observed sporadically within the TMJ discs. On the other hand, in the internal derangement specimens, CD34 was found frequently in the walls of blood capillaries within the TMJ discs. In the synovial membrane, CD34 was detected frequently in the walls of many blood capillaries in both the controls and the internal derangement specimens. Indeed, CD34 expression in internal derangement specimens was more intense than in control specimens. In the posterior loose connective tissue of the bilaminar zone, and in the anterior loose connective tissue between the upper and lower lamellae of the anterior capsular wall, CD34 was detected in abundance in the walls of blood capillaries both of the controls and the internal derangement specimens. Generally, CD34 was found rarely in the walls of large blood vessels. The presence of CD34 is suggested to be correlated with the process of angiogenesis induced by internal derangement of the TMJ.     

Analysis of 70Kd heat shock protein expression in patients with internal derangement of the temporomandibular joint

Recent studies have demonstrated that the expression of heat shock protein (HSP) was enhanced under stress in joint diseases, such as rheumatoid arthritis and osteoarthritis. The purpose of this study was to analyze the expression of 70Kd HSP in patients with internal derangement of the temporomandibular joint (TMJ) by immunohistochemical and enzyme-linked immunosorbent assay (ELISA) methods. For immunohistochemistry, 5 extirpated discs and 16 synovial biopsy specimens from patients with TMJ internal derangement and 2 extirpated discs from normal subjects were examined. For ELISA, synovial fluid from 11 patients with TMJ internal derangement and from 6 normal volunteers were investigated. The results showed that the 70Kd HSP staining intensity in chondrocytes around the damaged area of the articular discs from patients with TMJ internal derangement was higher than that in chondrocytes in control specimens. In addition, 70Kd HSP expression in synovial fluid from patients with TMJ internal derangement was slightly higher than that in normal subjects. These findings suggest that elevated 70Kd HSP expression is related to the progression of TMJ internal derangement.     

The expression of cyclooxygenase-2 in human temporomandibular joint samples: an immunohistochemical study

The aim of this investigation was to evaluate the immunohistochemical expression of cyclooxygenase-2 (COX-2) in the temporomandibular joint (TMJ) and to compare it with that control specimens. Expression of COX-2 in the TMJ disc and the synovial membrane in 26 human TMJ samples (internal derangement of TMJ; n=16, and control; n=10) was measured by an immunohistological technique using paraffin-embedded tissue and specific antihuman COX-2 polyclonal antibody. There were obvious distinction of COX-2 immunoreactivity between the control specimens and internal derangement cases, in the region of posterior and/or anterior loose connective tissues. In particular, intensive COX-2 expression was detected in the synovial membrane of internal derangement cases. The findings of the present study suggest that COX-2 might be an important mechanism regulating inflammation in the synovial membrane with internal derangement of TMJ.     

The localization of matrix metalloproteinase-3 and tenascin in synovial membrane of the temporomandibular joint with internal derangement

OBJECTIVES: The aim of this investigation was to study the immunohistochemical localization of MMP-3 and tenascin in the temporomandibular joint and to compare it with control specimens. MATERIALS AND METHODS: Localizations of matrix metalloproteinase-3 (MMP-3) and tenascin in the temporomandibular joint disc and the synovial membrane in 26 human temporomandibular joint samples (internal derangement of TMJ; n = 16, and control; n = 10) by an immunohistological method with monoclonal antibodies specific to human MMP-3 and tenascin. RESULTS: MMP-3 was not distributed in control specimens while it was observed in the internal derangement cases. MMP-3 showed two staining profiles: (1) diffuse staining was observed within the stroma of severely deformed disc with osteophyte and/or disc displacement (three of 16 specimens); and (2) the localization was specifically detected on the surface of severely hypertrophic synovial membrane (six of 16 specimens). The latter localization pattern resembled that of the tenascin on the surface of the severely hypertrophic synovial membrane. CONCLUSION: Comparative localization of MMP-3 and tenascin revealed intense staining for both in the synovial membrane presenting inflammation, proliferation and hypertrophy. These findings suggest that tissue repair and remodeling in the temporomandibular joint disc and the inflammatory hypertrophic reaction in the synovial membrane might proceed at the same time.     

Expression of vascular endothelial growth factor in human dysfunctional temporomandibular joint discs

A high density of blood vessels is found in specimens of temporomandibular joint (TMJ) disc at any stage of internal derangement of the joint, but the factors responsible for angiogenesis in the disc have not been described. The purpose here was to investigate, in human TMJ discs, the expression of vascular endothelial growth factor (VEGF), a multifunctional cytokine that contributes to angiogenesis. Specimens, free of significant morphological alterations and with varying degrees of disc tissue degeneration/regeneration, were studied by immunohistochemistry for VEGF in order to correlate immunohistochemical with histopathological findings. In normal discs and discs with minor pathological changes, fibroblast-like cells, fibrochondrocytes and chondrocyte-like cells were either not or only weakly immunostained by VEGF antibody. In disc specimens from internal derangement of the TMJ with significant tissue degeneration/regeneration, VEGF was consistently expressed. In these specimens, immunoreaction products for VEGF were observed both in the disc and in the endothelial cells of newly formed vessels. This VEGF immunolocalization is consistent with the stimulation of angiogenesis and the morphogenesis and differentiation of chondrocytes. Therefore VEGF expression by disc chondrocyte-like cells might reflect the action of the cytokine as an inducer of angiogenesis and as an autocrine signal for cells of the chondrogenic lineage.     

Immunohistochemical distribution of lymph capillaries and blood capillaries in the synovial membrane in cases of internal derangement of the temporomandibular joint

The distribution of lymph capillaries and blood capillaries in the synovial membrane was examined immunohistologically with anti–human collagen IV antibody and anti–human von Willebrand factor in 26 human temporomandibular joint (TMJ) samples comprising discs with adjoining synovial membrane from 10 control TMJs and from 16 TMJs with internal derangement. Three different distribution types were observed in the synovial membrane. In the control samples, the occurence of blood capillaries and lymph capillaries was rare. In mildly hyperplastic synovitis. lymph capillaries were observed just beneath the surface of the synovial membrane, whereas blood capillaries occurred in a little deeper layer of the synovia! membrane. In a severely hyperplastic synovitis. both lymph and Wood capillaries were observed frequently. The present results suggest that the different distribution patterns of lymph capillaries and blood capillaries reflect the degree of synovitis but can not be attributed to specific clinical symptoms.     

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.     

Bradykinin expression in synovial tissues and synovial fluids obtained from patients with internal derangement of the temporomandibular joint

Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of the potent pro-inflammatory properties. The purpose of this study is to investigate the expression of bradykinin in patients with internal derangement of the temporomandibular joint (TMJ). We examined 33 TMJ synovial biopsy specimens from 31 patients with internal derangement of the TMJ by an immunohistochemical technique using specific antibodies. We also determined the concentration of bradykinin in 20 synovial fluids from 18 patients with TMJ internal derangement by enzyme-linked immunosorbent assay. These data were compared with those of the control subjects. Bradykinin was predominantly localized in the synovial lining cell layer of TMJ samples obtained from patients with TMJ internal derangement. Bradykinin was also detected in 19 patients' TMJ synovial fluids and the average of bradykinin concentration in the synovial fluids of patients was higher than that of the healthy controls. Although a statistically significant correlation was not observed, these findings support the hypothesis that bradykinin may also be involved in the pathogenesis of TMJ pain and synovitis.     

Bradykinin Expression in Synovial Tissues and Synovial Fluids Obtained from Patients with Internal Derangement of the Temporomandibular Joint

Bradykinin has been implicated in the pathogenesis of inflammatory arthritis by virtue of the potent pro-inflammatory properties. The purpose of this study is to investigate the expression of bradykinin in patients with internal derangement of the temporomandibular joint (TMJ). We examined 33 TMJ synovial biopsy specimens from 31 patients with internal derangement of the TMJ by an immunohistochemical technique using specific antibodies. We also determined the concentration of bradykinin in 20 synovial fluids from 18 patients with TMJ internal derangement by enzyme-linked immunosorbent assay. These data were compared with those of the control subjects. Bradykinin was predominantly localized in the synovial lining cell layer of TMJ samples obtained from patients with TMJ internal derangement. Bradykinin was also detected in 19 patients' TMJ synovial fluids and the average of bradykinin concentration in the synovial fluids of patients was higher than that of the healthy controls. Although a statistically significant correlation was not observed, these findings support the hypothesis that bradykinin may also be involved in the pathogenesis of TMJ pain and synovitis.     

Localization of lymph capillaries and blood capillaries in human temporomandibular joint discs

The localization of lymph capillaries and blood capillaries in the human temporomandibular joint (TMJ) discs was examined immunohistologically with anti-human collagen IV antibody and anti-human von Willebrand factor in 26 human TMJ samples. The 16 internal derangement cases were then compared with the 10 normal control cases. The findings suggested that blood capillaries scarcely existed in all the fields of normal control TMJ discs (5/270, 1.9%) nor did lymph capillaries exist in the normal TMJ discs (0/270, 0%). New growth of blood capillaries had localized in all fields of the internal derangement discs specimens (113/378, 29.9%) and was concentrated in the lower area of the posterior part of the discs. The authors also observed a small distribution of lymph capillaries in all fields of this material (17/378, 4.5%). The new growth of lymph capillaries were always related to the blood capillary distribution and therefore their presence might be directly related to the capillary proliferation.     

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.     

Osteoarthritis and internal derangement of the temporomandibular joint: a light microscopic study

To describe osteoarthritic changes of the temporomandibular joint (TMJ) and their relation to internal derangements, 22 randomly selected TMJ autopsy specimens were dissected and studied by light microscopy. Normal disc position was seen in eight joints, partial anterior displacement of the discs in eight joints, and complete anterior displacement of the discs in five joints; one joint had a perforated disc. Degenerative changes, such as horizontal splitting, clustering of chondrocytes, bone marrow fibrosis, sclerosis, erosion, cyst formation, and reduction in TMJ size, were found in 11 of the 14 joints with displacement or perforation of the disc and in four of the eight joints with normal disc position. Internal derangement appeared to be associated with osteoarthritis. The relations between remodeling, aging, internal derangement, and osteoarthritis are discussed.     

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.     

Anchored disc phenomenon with a normally positioned disc in the temporomandibular joint: characteristics and behaviour

We aimed to elucidate the pathogenesis and evaluate the therapeutic behaviour of patients with an anchored disc phenomenon but a normally positioned disc of the temporomandibular joint (TMJ). Fourteen patients with internal derangement including closed lock of one TMJ were examined. All had normally positioned discs. Synovial fluid was collected from the TMJ by arthrocentesis. Their symptoms, and the protein concentration in the synovial fluid, were evaluated. Their median duration of illness was 3 months (range 0.5-12), and the median protein concentration was low (343 microg/ml; range 36-791). Arthrocentesis was successful in nine. Arthroscopic findings in the five unsuccessful cases showed severe intra-articular adhesions of the TMJ. The main intra-articular pathological feature was the presence of adhesions, which might be affected by low protein concentrations in the synovial fluid. These findings may provide a new treatment in patients with normally positioned discs, despite the small number studied.     

Magnetic resonance imaging evaluation of temporomandibular joint disc deformities in relation to type of disc displacement.

PURPOSE: This study was undertaken to assess the relationship between the temporomandibular joint (TMJ) disc deformity and the type of internal derangement. PATIENTS AND METHODS: One hundred thirty-three TMJs of 72 patients (53 female and 19 male) with intracapsular dysfunction were studied using clinical and magnetic resonance imaging examinations. RESULTS: Of the 133 TMJ discs, 41.35% had no deformity, whereas 18% of the discs were folded, 19.55% were lengthened, 9.77% were round, 7.51% were biconvex, and 3.75% had thick posterior bands. The frequency of disc deformity was greater with anterior disc displacement without reduction than in cases of anterior disc displacement with reduction (P <.001). Folded and round discs were most common in cases with TMJ anterior disc displacement without reduction (P <.0001). An increase in length was seen in 56.75% of the cases with anterior disc displacement with reduction, whereas 100% of nonreducing discs were mainly folded or rounded. Crepitation was correlated with folded and round disc deformities, whereas lengthening was the feature of reducing discs associated with early and intermediate clicking. CONCLUSIONS: The results show that the degenerative changes in the TMJ disc are influenced by the degree and the type of disc displacement. The more advanced the internal derangement, the more deteriorated the disc configuration.     

ADAMTS‐4 and ADAMTS‐5 expression in human temporomandibular joint discs with internal derangement,correlates with degeneration

Temporomandibular joint (TMJ) internal derangement (ID) is one of the most common form of temporomandibular disorders. There is evidence showing the increased expression of matrix metalloproteinases (MMPs) in the cells from degenerated TMJ disc. ADAMTS are a large family of metalloproteases which are responsible for proteoglycans degradation. The present study aimed to evaluate ADAMTS‐4 and ADAMTS‐5 immunohistochemical expression in human TMJ discs from patients affected by ID, and to find out if there is any correlation with the degree of histopathological changes. Eighteen temporomandibular displaced disc specimens and sixteen TMJ disc control were used for the present study. Specimens were immunohistochemically processed and ADAMTS‐4 and ADAMTS‐5 expression were obtained respectively for the anterior (AB), intermediate (IB) and posterior (PB) bands and compared to the histopathological degeneration score (HDS). Immunoreactivity for ADAMTS‐4 and ‐5, was observed in both not degenerated and degenerated human TMJ discs. Both the percentage of ADAMTS‐4 and ‐5 immunostained cells (ES) and the intensity of staining (IS) were significantly greater in affected specimens compared with those in control discs. The ADAMTS‐5 ES and IS of the 3 bands of the disc correlated to the TMJ disc HDS (0.001 < P < 0.05), on the other hand only AB and IB, ADAMTS‐4 immunostaining scores correlated to HDS. According to these findings it can be assumed in that the more histopathological changes in the disc are detected, the higher levels of ADAMTS are produced. This in turn can lead to ECM breakdown and in turn to a more advanced disc displacement.