Human TMJ Research Articles

Can TMJ morphological alterations impede TMJ agony?

Introduction: The relation between temporomandibular joint morphology and its incoordination is an arena which is not ventured in much even though many researches have been done but still it is a drop in the ocean of such a vast and complicated structure of the human TMJ anatomy. Objective: To evaluate morphological variations of temporomandibular joint in healthy and disorder patients using computed tomography. Study Design: A total of 20 temporomandibular joint disorder patients and 10 patients with normal TMJs and Class I occlusion were studied. The study was conducted at SUM Hospital and Oral Medicine and Radiology department, IDS Bhubaneswar with TMJ as chief complaint during a period from September 2016 to November 2016. Symptomatic group and asymptomatic group based on according to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/ TMD) were selected. The present research on TMJ morphology has been designed to investigate parameters like shape of condyle, glenoid fossa and articular eminence in relation to various temporomandibular disorders (TMD).The patients were enrolled with symptoms or signs such as pain, restricted mouth opening, deviation, clicking. A series of morphological parameters with teeth in maximum intercusspation were studied in CT scan. 

Correlation between FasL and IL-6 Expression in Human TMJ Disks with and without Osteoarthrosis

Correlation between FasL and IL-6 Expression in Human TMJ Disks with and without Osteoarthrosis

Identification of human temporomandibular joint fibrocartilage stem cells with distinct chondrogenic capacity

This study was aimed to identify the residence of human fibrocartilage stem cells (hFCSCs), characterize their stem cell properties and investigate the functional mechanisms which regulate fibrocartilage stem cells (FCSCs) toward chondrogenic differentiation during cartilage homeostasis and repairing. Cytological characteristics of hFCSCs and human orofacial mesenchymal stem cells (hOFMSCs) were analyzed. Chondrogenic potential of hFCSCs was compared with hOFMSCs both in vitro and in vivo. Regulatory role of SOX9 during FCSCs chondrogenesis was studied by shRNA interference in vitro, and by GFP+ FCSCs treatment in rat condylar cartilage defect model. SOX9 expression was also examined in temporomandibular joint osteoarthritis (TMJOA) patients' cartilage surface. hFCSCs exhibited typical mesenchymal stem cell characteristics, with significantly stronger chondrogenic capability compared to hOFMSCs. Moreover, hFCSCs showed remarkably increased expression of SOX9. During cartilage pellet culture, there was stronger SOX9 expression in hFCSCs than hOFMSCs. SOX9 shRNA interference downregulated chondrogenic capability of hFCSCs in vitro, as well as disrupting migration and chondrogenic differentiation of GFP+ FCSCs toward mature chondrocytes in rat condylar cartilage defect. Of note, SOX9 expression was also found suppressed in the condylar superficial zone of TMJOA patients. We found the existence of FCSCs in human TMJ cartilage, and characterized their distinct stem cell features. SOX9 is essential for hFCSCs chondrogenic differentiation, and a comprehensive understanding of the regulatory role of SOX9 in hFCSCs would be important for exploring potential intervention strategy of condylar cartilage degradation during TMJ disorders.

Evidence of vasculature and chondrocyte to osteoblast transdifferentiation in craniofacial synovial joints: Implications for osteoarthritis diagnosis and therapy.

Temporomandibular joint osteoarthritis (TMJ OA) leads to permanent cartilage destruction, jaw dysfunction, and compromises the quality of life. However, the pathological mechanisms governing TMJ OA are poorly understood. Unlike appendicular articular cartilage, the TMJ has two distinct functions as the synovial joint of the craniofacial complex and also as the site for endochondral jaw bone growth. The established dogma of endochondral bone ossification is that hypertrophic chondrocytes undergo apoptosis, while invading vasculature with osteoprogenitors replace cartilage with bone. However, contemporary murine genetic studies support the direct differentiation of chondrocytes into osteoblasts and osteocytes in the TMJ. Here we sought to characterize putative vasculature and cartilage to bone transdifferentiation using healthy and diseased TMJ tissues from miniature pigs and humans. During endochondral ossification, the presence of fully formed vasculature expressing CD31+ endothelial cells and α-SMA+ vascular smooth muscle cells were detected within all cellular zones in growing miniature pigs. Arterial, endothelial, venous, angiogenic, and mural cell markers were significantly upregulated in miniature pig TMJ tissues relative to donor matched knee meniscus fibrocartilage tissue. Upon surgically creating TMJ OA in miniature pigs, we discovered increased vasculature and putative chondrocyte to osteoblast transformation dually marked by COL2 and BSP or RUNX2 within the vascular bundles. Pathological human TMJ tissues also exhibited increased vasculature, while isolated diseased human TMJ cells exhibited marked increased in vasculature markers relative to control 293T cells. Our studyprovides evidence to suggest that the TMJ in higher order species are in fact vascularized. There have been no reports of cartilage to bone transdifferentiation or vasculature in human-relevant TMJ OA large animal models or in human TMJ tissues and cells. Therefore, these findings may potentially alter the clinical management of TMJ OA by defining new drugs that target angiogenesis or block the cartilage to bone transformation.

Immunohistochemical expression of TLR-4 in temporomandibular joint dysfunction

Objective Toll-like receptor 4 (TLR-4) is a transmembrane protein involved in the innate immune system and has been implicated in the pathogenesis of temporomandibular joint dysfunction (TMD). The purpose of this study was to histologically examine the level of expression of TLR-4 relative to severity of TMD.Methods Thirty-one human TMJ disc samples were immunostained for TLR-4 and evaluated for intensity of stain. Among the samples, 8 were control samples, 16 were from patients with anterior disc displacement with reduction (ADDwR), and 7 were from patients with anterior disc displacement without reduction (ADDwoR).Results There was no statistically significant difference in intensity of stain between groupings (p = 0.673).Conclusions The results indicate a negative correlation between TMD and the expression of TLR-4.

Regionally variant collagen alignment correlates with viscoelastic properties of the disc of the human temporomandibular joint

ObjectiveTo determine the regionally variant quality of collagen alignment in human TMJ discs and its statistical correlation with viscoelastic properties. DesignFor quantitative analysis of the quality of collagen alignment, horizontal sections of human TMJ discs with Pricrosirius Red staining were imaged under circularly polarized microscopy. Mean angle and angular deviation of collagen fibers in each region were analyzed using a well-established automated image-processing for angular gradient. Instantaneous and relaxation moduli of each disc region were measured under stress-relaxation test both in tensile and compression. Then Spearman correlation analysis was performed between the angular deviation and the moduli. To understand the effect of glycosaminoglycans on the correlation, TMJ disc samples were treated by chondroitinase ABC (C-ABC). ResultsOur imaging processing analysis showed the region-variant direction of collagen alignment, consistently with previous findings. Interestingly, the quality of collagen alignment, not only the directions, was significantly different in between the regions. The angular deviation of fiber alignment in the anterior and intermediate regions were significantly smaller than the posterior region. Medial and lateral regions showed significantly bigger angular deviation than all the other regions. The regionally variant angular deviation values showed statistically significant correlation with the tensile instantaneous modulus and the relaxation modulus, partially dependent on C-ABC treatment. ConclusionOur findings suggest the region-variant degree of collagen fiber alignment is likely attributed to the heterogeneous viscoelastic properties of TMJ disc that may have significant implications in development of regenerative therapy for TMJ disc.

ヒト顎関節滑膜細胞におけるMMP-1およびMMP-3産生に対するTNF- α の影響

ヒト顎関節滑膜細胞におけるMMP-1およびMMP-3産生に対するTNF- α の影響

Effects of cranberry components on IL-1β-stimulated production of IL-6, IL-8 and VEGF by human TMJ synovial fibroblasts

ObjectiveOsteoarthritis (OA) in the TMJ is characterized by deterioration of articular cartilage and secondary inflammatory changes. Interleukin-1β (IL-1β) stimulates IL-6, IL-8, and vascular endothelial growth factor (VEGF) in synovial fluid of TMJ with internal derangement and bony changes. The cranberry (Vaccinium macrocarpon) contains polyphenolic compounds that inhibit production of pro-inflammatory molecules by gingival cells in response to several stimulators. This study examined effects of cranberry components on IL-1β-stimulated IL-6, IL-8, and VEGF production by human TMJ synovial fibroblast-like cells. DesignCranberry high molecular weight non-dialyzable material (NDM) was derived from cranberry juice. Human TMJ synovial fibroblast-like cells from joints with degenerative OA and an ankylosed TMJ without degeneration were incubated with IL-1β (0.001–1nM)±NDM (25–250μg/ml) (2h preincubation). Viability was assessed via activity of a mitochondrial enzyme. IL-6, IL-8, and VEGF in culture supernatants were measured by ELISA; NF-κB and AP-1 transcription factors were measured in nuclear extracts via binding to specific oligonucleotides. Data analysis: ANOVA and Scheffe’s F procedure for post hoc comparisons. ResultsNDM did not affect cell viability but inhibited IL-1β stimulated IL-6, IL-8, and VEGF production in all cell lines (p<0.05). NDM partially reduced nuclear levels of NF-κB and AP-1 (p<0.04), depending upon cell line and time of exposure to IL-1β+NDM. ConclusionCranberry NDM inhibition of IL-1β-stimulated IL- 6, IL-8, and VEGF production by TMJ synovial fibroblast-like cells suggests that cranberry components may be useful as a host modulatory therapeutic agent to prevent or treat inflammatory arthropathies of the TMJ.

A Comparative Study of the Dentition and Temporomandibular Joint Anatomy and Histology Adult Dogs

Purpose: To describe and evaluate normal adult dog dentition and temporomandibular joint anatomically and histologically in comparison to humans. Method: Five adult dogs (6-12 months old) were used in this study. The following anatomical structures were histologically evaluated in a qualitative fashion: Teeth and related bony structures mandible, mandibular condyle, disc, Zygomatic arch, temporal bone, glenoid fossa, retrodiscal tissue and synovia. The macroscopical and microscopic study of the human TMJ was based on the current literature. Results: Dogs have three Incisors, one canine, four premolars, and 2 molars in the upper and 3 molars in the lower jaw. The TMJ is surrounded by a thin fibrous tissue capsule, and a synovial lining. The mandibular angle has a prominent shape. The glenoid fossa is flat, with extended mediolaterally with retroarticular process. Histologically, the TMJ is composed of different tissues that comprise the mandibular head, mandibular fossa and fibrocartilaginous disc. A layer of fibrous tissue covers the articulating cortical condyle and temporal bone followed by a layer of hyaline cartilage. Conclusion: Morphologically and numerically dog's teeth are different from humans. Morphologically and histologically, the articular structure of dogs is, on the whole, similar to that of humans. In these animals there is no articular eminence, but they have a retroarticular process.

β-defensin-3 and β-defensin-4 in synovial fluids from temporomandibular joints with osteoarthrosis

ObjectiveThis study aimed to analyze β-defensin-3 and β-defensin-4 in human TMJ synovial fluid obtained from patients affected by osteoarthritis (OA), in order to better understand the pathogenic mechanism that underlies this joint damage. Patients and methodsA total of 28 joints of 21 patients with diagnosis of OA were involved in the study group. Fourteen joints of 10 volunteers without signs or symptoms of TMJ diseases were used as the control group. The synovial fluid samples were collected from the superior joint cavity by the push-and-pull method. The supernatant was separated and stored in a deep freezer. The expression of β-defensin-3 and β-defensin-4 was evaluated by Western blot analysis. ResultsFindings obtained through Western blot showed that with respect to the control, both β-defensin-3 and β-defensin-4 were highly expressed (p<0.01) in OA TMJ synovial fluid; the expression of β-defensin-3 was very strong, while the β-defensin-4 was only strongly expressed. In control TMJ synovial fluid the band density observed was strikingly lower with respect to OA TMJ synovial fluid. ConclusionsAccording to the results obtained, here we hypothesize that β-defensins augment catabolic pathways in articular cartilage, ultimately leading to a timely breakdown of the extracellular matrix, and they participate in the degeneration of the articular cartilage and bone.

Analysis of chemokine production at TNF-α-stimulated synovial cells from human TMJ by antibody array

Analysis of chemokine production at TNF-<i>α</i>-stimulated synovial cells from human TMJ by antibody array

Effect of Mechanical Strain on Solute Diffusion in Human TMJ Discs: An Electrical Conductivity Study

This study investigated the effect of mechanical strain on solute diffusion in human TMJ discs (mean cadaver age 77.8) using the electrical conductivity method. The electrical conductivity, as well as small ion diffusivity, of male and female TMJ discs was determined under three compressive strains. In the male group, the average disc electrical conductivity (mean±SD) at 0% strain was 5.14±0.97mS/cm, decreased to 4.50±0.91mS/cm (-12.3%) at 10% strain, and 3.93±0.81mS/cm (-23.5%) at 20% compressive strain. Correspondingly, the average disc relative ion diffusivity at 0% strain was 0.44±0.08, decreased to 0.40±0.08 (-8.9%) at 10% strain, and 0.36±0.08 (-16.7%) at 20% compressive strain. In the female group, the average disc electrical conductivity at 0% strain was 5.84±0.59mS/cm, decreased to 5.01±0.50mS/cm (-14.2%) at 10% strain, and 4.33±0.46mS/cm (-25.8%) at 20% compressive strain. Correspondingly, the average disc relative ion diffusivity at 0% strain was 0.49±0.05, decreased to 0.43±0.04 (-11.3%) at 10% strain, and 0.39±0.04 (-19.9%) at 20% compressive strain. The results indicated that mechanical strain significantly impeded solute diffusion through the disc. This mechanical strain effect was larger in the female than in the male human TMJ disc. This study may provide new insights into TMJ pathophysiology.

ヒト顎関節摘出標本におけるCOX 1ならびにCOX 2の免疫組織化学的局在について

ヒト顎関節摘出標本におけるCOX 1ならびにCOX 2の免疫組織化学的局在について

Comparison between human and rat TMJ: anatomic and histopathologic features

To describe and evaluate normal rat temporomandibular joints from anatomic and histopathologic point of view and make a comparison between this joint in rats and humans. Twelve male adult Wistar rats (12 same side joints) were used in this procedure. The following anatomical structures were histologically evaluated in a qualitative fashion: condyle, disc, temporal bone, retrodiscal tissue and synovia. The macroscopical and microscopic study of the human TMJ was based on the current literature. The TMJ is surrounded by a thin capsule, consisting of fibrous tissue, and a synovial lining. The mandibular angle has a prominent shape. The glenoid fossa is flat, with no eminences. Histologically, the TMJ is composed of different tissues that comprise the mandibular head, mandibular fossa and fibrocartilaginous disc. A layer of hyaline cartilage covers the articulating cortical condyle and temporal bone. Morphologically and histologically, the articular structure of rats is, on the whole, similar to that of humans. In these animals there is no articular eminence.

387 PERIPATELLAR SYNOVITIS IN OSTEOARTHRITIS: COMPARISON OF NON-ENHANCED AND ENHANCED MAGNETIC RESONANCE IMAGING (MRI) AND ITS ASSOCIATION WITH PERIPATELLAR KNEE PAIN. THE MOST STUDY

Results: The cartilage tissue in the human TMJ was clearly visible and distinguishable from bone after contrast enhancement with Optiray (Fig. 1a, 1b). Furthermore, three-dimensional bone reconstructions enabled quantitative analysis and detection of bone abnormalities (Fig. 1c). Easy discrimination between cartilage and SCB allowed for separate visualization in 3D reconstruction and for measures on cartilage thickness (Fig. 1b, 1d). The average cartilage thickness was 0.33±0.04mm (range: 0.28−0.36mm) and 0.32±0.22mm (range: 0.072−0.695mm) for the healthy and OA-classified samples, respectively. Conclusions: The present study provides new information about the application of Optiray as a tool to visualize both bone and cartilage tissue in TMJ reconstructions obtained with a mCT system. This combined method makes quantitative measures of both articular cartilage and the underlying bone possible at high resolution. To our knowledge, this is the first time simultaneous assessment of bone and cartilage components has been performed in the human TMJ. With the presented methodology a direct relationship between OA-like features in bone and cartilage can be established. Furthermore, this method can be used for the development of large scale finite element models for the examination of the biomechanical interaction between articular cartilage and SCB in both a healthy and OA situation.

The role of hypoxia on expression of cyclooxygenase-2 in synovial fibroblasts derived from human temporomandular joint

To investigate the effects of hypoxia on expression of COX-2 in synovial fibroblasts derived from human TMJ and to analyze the biological role of COX-2 on TMJ disorders. Synovial fibroblasts were induced by hypoxia, COX-2 expression was determined by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Moreover, cells were stimulated by hypoxia or celecoxib or both of them, prostaglandin E(2) (PGE(2)), matrix metalloproteinase 2, 9 (MMP-2, MMP-9) release was detected by enzyme-linked immunosorbent assay (ELISA) or gelatin zymography. Cells that were placed under normoxic conditons were used as controls. (1) In response to hypoxia, at 4 h (1.51 +/- 0.34), 8 h (1.39 +/- 0.57), significant elevation of COX-2 mRNA expression occurred, compared with data (0.65 +/- 0.24), (0.71 +/- 0.15) under normoxic condition (both P < 0.05). (2) The elevation of COX-2 protein was detectable at 6 h (0.29 +/- 0.06), 12 h (0.51 +/- 0.09), 24 h (0.68 +/- 0.11), contrasted with normoxia (all P < 0.01). Therefore, it is suggested that COX-2 expression pattern present a time-dependent response to hypoxic conditions. (3) The concentration of PGE(2) released by synovial fibroblasts under 12 h hypoxic condition (7.6 ng/ml +/- 0.8 ng/ml) was significantly higher than those under normoxic condition (2.5 ng/ml +/- 0.4 ng/ml, P < 0.01) or in response to celecoxib combined with hypoxia (4.3 ng/ml +/- 0.4 ng/ml, P < 0.05). (4) The amount of MMP-2, MMP-9 produced by synovial fibroblasts under 12 h hypoxic condition was upregulated compared with that under normoxia or in response to celecoxib combined with hypoxia. Hypoxia is, at least in part, responsible for the pathogenesis of TMJ disorders, probably by promoting COX-2 expression of synovial fibroblasts derived from TMJ.

Effects of low-level laser irradiation in cultured synovial cells from human TMJ

Effects of low-level laser irradiation in cultured synovial cells from human TMJ

Expression of heat shock protein 27 (HSP27) in human temporomandibular joint discs of patients with internal derangement.

Heat shock proteins (HSPs) are believed to represent a cellular stress response mechanism that protects intracellular proteins from damaging events. Some studies have demonstrated an enhanced expression of large-molecular-weight HSPs in diseased systematic joints. Small heat shock proteins, and among these HSP27, have been studied to a lesser extent. HSP27 has cytoprotective and biosynthetic functions within chondrocytes, and it is an estrogen-associated protein that is under hormonal modulation. To improve understanding at a molecular level of the pathophysiology of certain temporomandibular joint disorders, the authors carried out this immunohistochemical study to assess the presence of HSP27 in human TMJ discs. Twelve adult human TMJ discs (10 diseased and 2 healthy discs) and 5 TMJ fetal human discs were used in this study. Adult discs and TMJ tissues of human fetuses were fixed in 10% buffered formalin. Samples were then processed for histologic examination. Sections were immunohistochemically stained using the streptavidin-biotin detection method. No reaction product for HSP27 in the discs of fetuses was noted. HSP27 was weakly expressed in normal TMJ discs and highly up-regulated in discs of patients showing new vessel formation and chondroid metaplasia. Any correlation between gender and HSP27 was found in the sample, being the up-regulation of HSP27 related mostly to major histopathological changes. This different pattern of HSP27 immunostaining in human TMJ discs detected in the authors' specimens suggests that the expression of this small HSP is functionally modulated. In fact HSP27 up-regulates in internal derangement specimens with major histopathological changes; on the other hand, it is not expressed or only weakly expressed in TMJ discs of fetuses and normal TMJ discs.

Discussion

The authors' observation of the presence of elastic and oxytalan fibers running parallel to the collagen bundles in the human temporomandibular disc confirms our prior observation using similar staining methods. 1 Helmy E Larke V Bays R et al. Identification of elastic and oxytalan fibers in human cadaver TMJ. J Dent Res. 1984; 63: 228 Google Scholar Unlike the course and much more abundant elastic fibers in the bilaminar zone and collateral ligaments, the elastic fibers in normal human discs are much finer and require higher magnification to visualize under the light microscope 1 Helmy E Larke V Bays R et al. Identification of elastic and oxytalan fibers in human cadaver TMJ. J Dent Res. 1984; 63: 228 Google Scholar .

Identification of Chlamydia trachomatis in the human temporomandibular joint.

Reactive arthritis (ReA) as a consequence of triggering Chlamydia trachomatis infections has been extensively studied to better understand inflammatory arthritis. This study investigated whether the presence of C trachomatis can be shown in the TMJ of patients with internal derangement. Posterior bilaminar tissue removed from 31 patients (29 F, 2 M) during TMJ articular disc repositioning and posterior ligament repair was tested for the presence of C trachomatis. Cryosections were stained using a monoclonal antibody that identifies all chlamydial serovars. Highly specific polymerase chain reaction (PCR) assays independently targeting two genes of C trachomatis also were performed; these assays also identify all serovars of this organism. TMJ tissue from 6 of 30 patients (20%) showed the presence of C trachomatis in the posterior bilaminar tissue on immunostaining. PCR screening identified 12 of 31 patients (39%) as having C trachomatis DNA in tissue, including four of six positive by immunostaining. All chlamydia-positive patients were female, with an average age of 36.7 years (15 to 48 years). The presence of C trachomatis in the human TMJ has not been previously shown. The presence of this organism may serve as the pathogenetic mechanism for TMJ dysfunction, as demonstrated in other joints. Nonapparent chlamydial infection in females may also explain the marked prevalence of TMJ symptoms in women.