Serotonin in an antigen-induced arthritis of the rabbit temporomandibular joint.

The aim was to investigate the joint perfusate concentration of serotonin (5-HT) in antigen-induced monoarthritis of the rabbit temporomandibular joint (TMJ) and knee joint. Thirty adult male New Zealand White rabbits, of whom eight were first used as healthy controls, were divided into TMJ and knee arthritis groups. Unilateral arthritis was induced with ovalbumin intra-articularly and the contralateral joint was sham-induced. The joints were perfused with saline (flow rate, 0.05 ml/min; 10-min intervals during 50 min) 3 weeks later and the 5-HT concentration analysed. After the perfusion, the joints were evaluated histologically. The 5-HT concentration in the initial perfusate from the arthritic TMJ was higher than in both sham-induced and healthy control joints, and from the knee joint arthritis higher than in sham-induced joints. No histological difference in the arthritis was observed between the two groups. This study shows that the 5-HT concentration found immediately after puncture is increased in antigen-induced arthritis of the rabbit TMJ and knee joint.     

Immunohistochemical study of interleukin-1beta and interleukin-1 receptor antagonist in an antigen-induced arthritis of the rabbit temporomandibular joint.

BACKGROUND: In temporomandibular joint (TMJ) arthritis, there is limited knowledge of the relationship between interleukin-1beta (IL-1beta) and interleukin-1 receptor antagonist (IL-1ra), as well as the source of these cytokines. We investigated the development of an antigen-induced arthritis in the rabbit TMJ immunohistochemically. METHODS: Unilateral TMJ arthritis was induced in 32 adult New Zealand White rabbits. From 6 h to 12 weeks after induction of arthritis, topology of IL-1beta and IL-1ra were observed. RESULT: The acute stage of induced arthritis lasted for one week after induction, thereafter it became chronic. In the early phase of the acute stage, infiltrating inflammatory cells, as well as synovial cells, produced IL-1beta and IL-1ra. In the late phase of the acute stage, the main source of these cytokines was subsynovial fibroblasts. In this phase of arthritis, IL-1beta and IL-1ra did not appear to be produced by synovial cells. From the early to intermediate phase of the chronic stage, proliferating synovial cells produced IL-1beta and IL-1ra. In this phase of the arthritis, these cytokines were also observed in a cluster formation in chondrocytes. CONCLUSION: This arthritis model shows a staging of the joint inflammation process with time. IL-1beta and IL-1ra are produced by a certain kind of cells depending on the stage of inflammation.     

Relationship between TNF-α and TUNEL-positive chondrocytes in antigen-induced arthritis of the rabbit temporomandibular joint

BACKGROUND: Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick end-labeling (TUNEL) staining is a widely accepted method for the detection of DNA fragmentation in nuclei of apoptotic cells. Tumor necrosis factor (TNF)-alpha is closely associated with changes in condylar cartilage and modulates apoptosis in various tissues including cartilage. The aim of this study was to investigate the relationship between apoptotic chondrocytes and TNF-alpha in a rabbit model of arthritis. METHOD: Unilateral temporomandibular joint (TMJ) arthritis was induced in 20 adult New Zealand White rabbits. From 1 day to 6 weeks after the induction of arthritis, immunohistochemical analysis for TNF-alpha and TUNEL was performed. RESULTS: In condylar cartilage, TNF-alpha-positive cells and TUNEL-positive cells were localized together. TNF-alpha-positive chondrocytes seemed to precede TUNEL-positive cells. CONCLUSIONS: The results of the present study suggest that TNF-alpha may be involved in apoptosis and/or apoptotic necrosis of chondrocytes as TMJ arthritis progresses from the acute to chronic stage.     

Involvement of tumor necrosis factor-α and interleukin-8 in antigen-induced arthritis of the rabbit temporomandibular joint

BACKGROUND: In temporomandibular joint (TMJ) arthritis, knowledge is limited about the source of the inflammatory mediators. The aim of this study was to investigate the immunohistochemical role of tumor necrosis factor-alpha (TNF-alpha) and interleukin-8 (IL-8) in the development of the antigen-induced arthritis of the rabbit TMJ. METHODS: Unilateral TMJ arthritis was induced in 28 adult rabbits. From 6 h to 6 weeks after induction of arthritis, the topology of TNF-alpha and IL-8 was observed. RESULTS: Positive reaction for TNF-alpha of synovial cells was observed within 3 days after induction and at 3 weeks after induction. TNF-alpha positive vascular endothelial cells and chondrocytes were identified throughout the observation period. IL-8 was detected only during the acute stage. CONCLUSIONS: The cytokines TNF-alpha and IL-8 were observed in specific cells depending on the stage. TNF-alpha was particularly related with angiogenesis and cartilage destruction and IL-8 was involved in the acute stage of inflammation.     

Local effects of intra-articular injection of anti-rabbit tumor necrosis factor alpha monoclonal antibody in antigen-induced arthritis of the rabbit temporomandibular joint

J Oral Pathol Med (2012) 41 : 96–105 Background: Local effects of intra‐articular (IA) injection of anti‐rabbit tumor necrosis factor alpha monoclonal antibody (anti‐TNFα mAb) for antigen‐induced mono‐arthritis (AIA) of the rabbit temporomandibular joint (TMJ) and its systemic influences were evaluated. Methods: Biochemical analysis of synovial fluid (SF), clinical and histopathological analyses of TMJ, and serum analysis were performed after inducing AIA in bilateral TMJs of 40 New Zealand White rabbits. IA injection of anti‐TNFα mAb in unilateral TMJ (TNF blockade side; n = 12) and IgG (n = 12) was performed while saline injected on the contralateral side. TNFα and IL‐1β in SF was analyzed at Days 1, 3, 7, and 21. Joint swelling and head withdrawal reflex threshold (WRT) over TMJs were evaluated in TNF blockade side (n = 12) with histopathological analysis at Days 3, 7, and 21. In remaining four animals with TNF blockade, TNFα and anti‐TNFα mAb in serum were analyzed. Results: Tumor necrosis factor alpha in SF was significantly lower in TNF blockade side on all days but IL‐1β was lower only on Day 3. WRT was significantly higher at all times in the blockade side. Less inflammatory reactions and degenerative changes of cartilage were observed on Days 7 and 21 in the blockade side. TNFα and anti‐TNFα mAb were under detection level in serum at all times. Conclusions: Intra‐articular injection of anti‐rabbit TNFα mAb in mono‐arthritis model was effective to control local inflammation and degenerative joint changes. Further, low‐dose IA injection of antibody may not have systemic side effects.     

Therapy of antigen-induced arthritis of the temporomandibular joint via platelet-rich plasma injections in domestic pigs

The aim of this animal study was to investigate the effect of platelet-rich plasma (PRP) injections into the temporomandibular joint (TMJ) to treat antigen-induced arthritis AIA.AIA was induced via the application of bovine serum albumin (BSA) into the TMJ. Clear histological signs and protein analysis results indicating inflammation of the TMJ were observed. Afterwards, two PRP injections were performed over an interval of 2 weeks.Concentration levels of the proinflammatory cytokines IL-1β (PRP: 33.7 ± 5.6 pg/mg, untreated: 50.0 ± 2.9 pg/mg; p = 0.04) and TNF-α (PRP: 20.7 ± 2.5 pg/mg, untreated: 31.4 ± 2.7 pg/mg; p = 0.03) were significantly decreased in the PRP-treated joints. A significant reduction in signs of histological inflammation, such as hyperplasia of the synovial membrane, leucocyte infiltration, cartilage surface alterations, and an increase in cartilage-specific glycosaminoglycan content, was observed.This animal study supports the understanding of the underlying effects of PRP treatment in the TMJ, and may enhance novel PRP therapies in the future.     

Clinical course of an antigen induced arthritis model in the rabbit temporomandibular joint

The aim of this study was to investigate clinical features of an antigen-induced arthritis model in the rabbit temporomandibular joint (TMJ) and compare them to those in knee joint (KJ) arthritis. Eighteen adult male New Zealand White rabbits were divided into a TMJ arthritis group and a KJ arthritis group. Monoarthritis was induced unilaterally with ovalbumin and clinical observations, including joint swelling, skin surface temperature (SST) over the joints, and the withdrawal reflex threshold (WRT) to noxious pressure, were performed over a 3 week period. The joints were then evaluated histologically. The WRT was decreased during the 3 weeks after induction of TMJ arthritis, together with mild but significant joint swelling. The arthritic KJ also showed significant swelling and reduced WRT during the 3 week period. A significant increase of SST over the arthritic TMJ was present during the first week, while changes in SST over the KJ were inconsistent. The histological evaluation showed chronic arthritic features in all arthritic joints of both groups and no difference in the severity of arthritis was found between the TMJ and the KJ.     

Cytokines in temporomandibular joint arthritis

As the article in the current issue by Shinoda and colleagues shows, during the last two decades, there has been a dramatic increase in the understanding of basic biology behind chronic temporomandibular joint (TMJ) pain, inflammation and destruction. The involvement and contribution of cytokines to TMJ pain and inflammation must now be considered as established, evident and fundamental. Based on the present knowledge, it is now possible to design and investigate novel therapeutic strategies. These new and very encouraging approaches include manipulation of cytokine function, immune reactivity and the behaviour of inflammatory cells while maintaining the integrity of the affected tissue.     

Arthroscopy of the rabbit temporomandibular joint

Arthroscopy of the rabbit temporomandibular joint was evaluated experimentally on 22 rabbits. A small arthroscope with so-called "Selfoc"-system was employed. The reaction to arthroscopy was analyzed clinically. Macroscopic dissection and histology were then employed to detect possible pathological changes in the joints at periodic intervals. The established criteria for evaluation of postoperative reactions were erythema, suppuration, weight changes and chewing capacity. The results of this study indicate that the rabbit temporomandibular joint may be arthroscoped with subsequent minor reversible changes. It also seems feasible to assume that temporomandibular joint arthroscopy in humans runs a low risk for postoperative complications.     

Involvement of the temporomandibular joint in rheumatoid arthritis

The rheumatoid arthritis is a systemic connective tissue disease, that most of the cases involve the temporomandibular joint. The diagnosis of local involvement is usually not difficult because the disease often starts in other peripheral small joints. The radiographic signs can be observed more frequently than clinical and subjective symptoms. The local symptoms are pain, opening difficulty, stiffness in the morning and swelling. The maximal mouth opening is restricted by the reduced translatory movement of the mandibular condyle. The aim of this case presentation is to describe the temporomandibular aspects of the rheumatoid arthritis and to suggest the usefulness of the condylar movement registration in the diagnostic procedure of the disease.     

Clinical diagnosis of temporomandibular joint arthritis

Evidence‐based clinical diagnostic criteria for temporomandibular joint (TMJ) arthritis are not available. To establish (i) criteria for clinical diagnosis of TMJ arthritis and (ii) clinical variables useful to determine inflammatory activity in TMJ arthritis using synovial fluid levels of inflammatory mediators as the reference standard. A calibrated examiner assessed TMJ pain, function, noise and occlusal changes in 219 TMJs (141 patients, 15 healthy individuals). TMJ synovial fluid samples were obtained with a push–pull technique using the hydroxycobalamin method and analysed for TNF, TNFsRII, IL‐1β, IL‐1ra, IL‐1sRII, IL‐6 and serotonin. If any inflammatory mediator concentration exceeded normal, the TMJ was considered as arthritic. In the patient group, 71% of the joints were arthritic. Of those, 93% were painful. About 66% of the non‐arthritic TMJs were painful to some degree. Intensity of TMJ resting pain and TMJ maximum opening pain, number of jaw movements causing TMJ pain and laterotrusive movement to the contralateral side significantly explained presence of arthritis (AUC 0.72, P < .001). Based on these findings, criteria for possible, probable and definite TMJ arthritis were determined. Arthritic TMJs with high inflammatory activity showed higher pain intensity on maximum mouth opening (P < .001) and higher number of painful mandibular movements (P = .004) than TMJs with low inflammatory activity. The combination TMJ pain on maximum mouth opening and Contralateral laterotrusion <8 mm appears to have diagnostic value for TMJ arthritis. Among arthritic TMJs, higher TMJ pain intensity on maximum mouth opening and number of mandibular movements causing TMJ pain indicates higher inflammatory activity.     

Psoriatic arthritis and the temporomandibular joint.

The clinical and radiological changes produced by psoriatic arthritis in the temporomandibular joints of 7 patients are described. There are few references in the literature to such changes, owing, perhaps, to the comparative rarity of this condition and to the difficulty of examining these joints radiologically. The possibility of the progression of Reiter's disease to psoriatic arthritis is mentioned. The changes described are in many ways similar to those produced by rheumatoid arthritis. It is important that patients who display such abnormalities but are known not to be suffering from rheumatoid arthritis should be properly investigated for psoriatic arthritis.     

Arthroscopy of the temporomandibular joint of the rabbit.

A technique for arthroscopic examination of the temporomandibular joint (TMJ) of the rabbit is reported. Rabbits were selected because of the accessibility of the joint and its relative morphologic similarity to the human TMJ. The clinical findings and postoperative sequelae of the procedure are discussed. The results indicate that the technique safely and accurately demonstrates the internal anatomy of the TMJ, and suggest its future application in studies in humans.     

Interleukin-1 beta, interleukin-6, and tissue inhibitor of metalloproteinase-1 in the synovial fluid of the temporomandibular joint with respect to cartilage destruction

OBJECTIVE: The distribution and biological roles of interleukin (IL)-1 beta, IL-6, and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the synovial fluid of patients with non-inflammatory chronic temporomandibular joint (TMJ) disorders were evaluated in relation to pain upon joint movements and X-ray and magnetic resonance imaging (MRI) findings. MATERIALS AND METHODS: TMJ aspirates were obtained from 48 patients (48 joints) with chronic TMJ disorders and from 18 controls (18 joints). The IL-1 beta and IL-6 levels in the aspirates were determined by using an enzyme-linked immunosorbent assay and the TIMP-1 level was measured by an enzyme immunoassay. Following examinations for pain upon joint movements and X-ray and MRI observations, the IL-1 beta, IL-6, and TIMP-1 levels and frequencies of their detection were compared. RESULTS: The IL-1 beta level and frequency of detection showed no correlation with pain upon joint movements or with the X-ray and MRI findings. In the frequency of detection of IL-6, there were significant differences between control (no detection) and all chronic TMJ disorder groups that were classified by imaging diagnosis (P < 0.001). A correlation was also noted between the presence of IL-6 and pain upon joint movements. The IL-6 level was correlated with the TIMP-1 level and with pain upon joint movements. TIMP-1 level was correlated with pain upon joint movements. The TIMP-1 was present in higher level from patients with chronic TMJ disorders who exhibited osseous changes on the X-ray images. CONCLUSION: The results indicated that the IL-6 and TIMP-1 levels in the TMJ aspirates of patients with chronic TMJ disorders have been raised. The former was not detected in the TMJ aspirates of the control. These findings suggest that IL-6 and TIMP-1 might play a role in the etiology of chronic TMJ disorders, but further studies are needed to validate this.