Synovial fluid of the joint decreases friction between the cartilage surfaces and reduces cartilage wear during articulation. Characteristic changes of synovial fluid have been shown in patients with osteoarthritis (OA) in the temporomandibular joint (TMJ). OA is generally considered to be induced by excessive mechanical stress. However, whether the changes in synovial fluid precede the mechanical overloading or vice versa remains unclear. In the present study, our purpose was to examine if the breakdown of joint lubrication affects the frictional properties of mandibular condylar cartilage and leads to subsequent degenerative changes in TMJ. We measured the frictional coefficient in porcine TMJ by a pendulum device after digestion with hyaluronidase (HAase) or trypsin. Gene expressions of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), matrix metalloproteinases (MMPs), type II collagen, and histology were examined after prolonged cyclic loading by an active pendulum system. The results showed that the frictional coefficient increased significantly after HAase (35%) or trypsin (74%) treatment. Gene expression of IL-1β, COX-2, and MMPs-1, -3, and -9 increased significantly in enzyme-treated TMJs after cyclic loading. The increase in the trypsin-treated group was greater than that in the HAase-treated group. Type II collagen expression was reduced in both enzyme-treated groups. Histology revealed surface fibrillation and increased MMP-1 in the trypsin-treated group, as well as increased IL-1β in both enzyme-treated groups after cyclic loading. The findings demonstrated that the compromised lubrication in TMJ is associated with altered frictional properties and surface wear of condylar cartilage, accompanied by release of pro-inflammatory and matrix degradation mediators under mechanical loading.

Excessive mechanical stimulation is considered an important factor in the destruction of chondrocytes. Focal adhesion kinase (FAK) is non-receptor tyrosine kinase related to a number of different signaling proteins. Little is known about the function of FAK in chondrocytes under mechanical stimulation. In the present study, we investigated the function of FAK in mechanical signal transduction and the mechanism through which cyclic tensile strain (CTS) induces expression of inflammation-related factors. Mouse ATDC5 chondrogenic cells were subjected to CTS of 0.5 Hz to 10% cell elongation with an FAK inhibitor. The expression of genes encoding COX-2, IL-1β, and TNF-α was examined using real-time RT-PCR after CTS application with FAK inhibitor. Phosphorylation of p-38, ERK, and JNK was analyzed by Western blotting. Differences in COX-2 expression following pretreatment with FAK, p-38, ERK, and JNK inhibitors were compared by Western blotting. We found that CTS increased the expression of genes encoding COX-2, IL-1β, and TNF-α and activated the phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with an FAK inhibitor for 2 h reduced the expression of genes encoding COX-2, IL-1β, and TNF-α induced by CTS-associated inflammation and decreased phosphorylation of FAK, p-38, ERK, and JNK. Pretreatment with FAK, p-38, ERK, and JNK inhibitors markedly suppressed COX-2 and IL-1β protein expression. In conclusion, FAK appears to regulate inflammation in chondrocytes under CTS via MAPK pathways.

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This article was designed to report the current status of temporomandibular joint disorders (TMDs) and the therapeutic system on the basis of a series of clinical, biomechanical, histological and biochemical studies in our research groups. In particular, we have focused on the association of degenerative changes of articular cartilage in the mandibular condyle and the resultant progressive condylar resorption with mechanical stimuli acting on the condyle during the stomatognathic function. In a clinical aspect, the nature and prevalence of TMDs, association of malocclusion with TMDs, association of condylar position with TMDs, association of craniofacial morphology with TMDs, and influences of TMDs, TMJ-osteoarthritis (TMJ-OA) in particular, were examined. In a biomechanical aspect, the nature of stress distribution in the TMJ from maximum clenching was analyzed with finite element method. In addition, the pattern of stress distribution was examined in association with varying vertical discrepancies of the craniofacial skeleton and friction between the articular disk and condyle. The results demonstrated an induction of large compressive stresses in the anterior and lateral areas on the condyle by the maximum clenching and the subsequent prominent increases in the same areas of the mandibular condyle as the vertical skeletal discrepancy became more prominent. Increase of friction at the articular surface was also indicated as a cause of larger stresses and the relevant disk displacement, which further induced an increase in stresses in the tissues posterior to the disks, indicating an important role of TMJ disks as a stress absorber. In a histological or biological aspect, increase in TMJ loading simulated by vertical skeletal discrepancy, which has already been revealed by the preceding finite element analysis or represented by excessive mouth opening, produced a decrease in the thickness of cartilage layers, an increase in the numbers of chondroblasts and osteoclasts and the subsequent degenerative changes in the condylar cartilage associated with the expression of bone resorption-related factors. In a biochemical or molecular and cellular aspect, excessive mechanical stimuli, irrespective of compressive or tensile stress, induced HA fragmentation, expression of proinflammatory cytokines, an imbalance between matrix metalloproteinases and the tissue inhibitors, all of which are assumed to induce lower resistance to external stimuli and degenerative changes leading to bone and cartilage resorption. Excessive mechanical stimuli also reduced the synthesis of superficial zone protein in chondrocytes, which exerts an important role in the protection of cartilage and bone layers from the degenerative changes. It is also revealed that various cytoskeletal changes induced by mechanical stimuli are transmitted through a stretch-activated or Ca2+ channel. Finally, on the basis of the results from a series of studies, it is demonstrated that optimal intra-articular environment can be achieved by splint therapy, if indicated, followed by occlusal reconstruction with orthodontic approach in patients with myalgia of the masticatory muscles, and TMJ internal derangement or anterior disk displacement with or without reduction. It is thus shown that orthodontic treatment is available for the treatment of TMDs and the long-term stability after treatment.

Clinical trial number: REG1464069