This paper reviews recent findings of the synovial membrane, in particular the morphology, function and development of synovial lining cells, in the temporomandibular joint (TMJ). Electron microscopic studies have confirmed the synovial membrane in TMJ consists of macrophage-like type A cells and fibroblast-like type B cells identical to those in other systematic joints. The macrophage-like type A cells react with anti-macrophage and macrophage-derived substances including the major histocompatibility class II molecule, and show a drastic increase in their number in the inflamed synovial membrane. In addition, they have the ability to produce substances involved in the progression of TMJ inflammation such as nitric oxide and inducible nitric oxide synthase. Observation of osteopetrotic mice revealed that macrophage-like type A cells in TMJ are derived from monocyte lineage. Immunocytochemistry for 25kDa heat shock protein was able to depict the entire shape of fibroblast-like type B cells including their unique processes. The expression of an estrogen receptor alpha-immunoreaction in the fibroblast-like type B cells may explain the etiology of temporomandibular disorders at a higher frequency in females than in males, suggesting that TMJ is a target tissue for estrogen. Furthermore, fibroblast-like type B cells are equipped with a basement membrane to serve as an adhesion molecule for the fibroblast-like type B cells to keep their epithelial arrangement. A clear understanding of the morphology of the intact synovial membrane will serve to clarify the etiology and development of temporomandibular disorders.
BackgroundMolecular biomarkers are essential for monitoring treatment effects, predicting prognosis, and improving survival rate in oral squamous cell carcinoma. This study sought to verify the effectiveness of two integrin gene expression ratios as biomarkers.MethodsGene expression analyses of integrin α3 (ITGA3), integrin β4 (ITGB4), CD9 antigen (CD9), and plakoglobin (JUP) by quantitative real-time PCR were conducted on total RNA from 270 OSCC cases. The logrank test, Cox proportional hazards model, and Kaplan-Meier estimates were performed on the gene expression ratios of ITGA3/CD9 and ITGB4/JUP and on the clinicopathological parameters for major clinical events.ResultsA high rate (around 80%) of lymph node metastasis was found in cases with a high ITGA3/CD9 ratio (high-ITGA3/CD9) and invasive histopathology (YK4). Primary site recurrence (PSR) was associated with high-ITGA3/CD9, T3-4 (TNM class), and positive margin, indicating that PSR is synergistically influenced by treatment failure and biological malignancy. A high ITGB4/JUP ratio (high-ITGB4/JUP) was revealed to be a primary contributor to distant metastasis without the involvement of clinicopathological factors, suggesting intervention of a critical step dependent on the function of the integrin β4 subunit. Kaplan-Meier curves revealed positive margin as a lethal treatment consequence in high-ITGA3/CD9 and YK4 double-positive cases.ConclusionTwo types of metastatic trait were found in OSCC: locoregional dissemination, which was reflected by high-ITGA3/CD9, and distant metastasis through hematogenous dissemination, uniquely distinguished by high-ITGB4/JUP. The clinical significance of the integrin biomarkers implies that biological mechanisms such as cancer cell motility and anchorage-independent survival are vital for OSCC recurrence and metastasis.
This study aimed to determine whether psychophysical stress conditionings had facilitatory effects on masseter muscle nociception in the central nervous system via serotonergic mechanisms in rats. Two experiments were conducted to assess: (1) whether repeated forced swim stress for 3 days increased the number of Fos-positive neurons evoked by masseter muscle injury due to formalin injection; and (2) whether serotonin-reuptake inhibitor, fluoxetine, administered daily after each stress conditioning, had modulatory roles on Fos expression. The number of Fos-positive cells was quantified in several areas within the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord regions (Vc areas), including the ventrolateral area of the trigeminal subnucleus interpolaris/Vc transition, and the middle or caudal portion of the Vc regions, since nociceptive neural activity in the Vc region could play critical roles in deep craniofacial nociception. We found that forced swim stress conditionings increased depression-like behaviors, which was prevented by fluoxetine. Repeated forced swim stress significantly increased Fos expression in all Vc areas compared with those of non-stressed rats, while systemic administration of fluoxetine significantly decreased Fos expression in all areas, but mainly in the caudal Vc region, in stressed rats. Fluoxetine had no effect on Fos expression in non-stressed rats. These results indicate that repeated forced swim stress conditionings increase Fos expression in the Vc areas, and the contribution of serotonergic mechanisms to masseter muscle nociception could be greater in stressed rats than in sham rats. These results support the hypothesis that changes in brain function, including serotonergic mechanisms, in the Vc areas play critical roles in enhanced masseter muscle nociceptive responses under psychophysical stress conditions.
The synovial lining layer of the temporomandibular joint (TMJ) consists of macrophage-like type A cells and fibroblastlike type B cells. Until now, little information has been available on the development of the synovial membrane in TMJ. In the present study we examined the development of the synovial lining layer in the rat TMJ by light-and electron-microscopic immunocytochemistry for heat shock protein (Hsp) 25, which is a useful marker for type B cells. At embryonic day 19 (E19), a few Hsp25-positive cells first appeared in the upper portion of the developing condyle. During the formation of the upper articular cavity (E21 to postnatal day 1 (P1)), a few positive cells were arranged on its surface. Immunoelectron microscopy demonstrated that these cells had ultrastructural features of fibroblast-like type B cells. In addition, some Hsp25-positive cells moved to the deep portion by extending their cytoplasmic processes toward the articular cavity at P3. At that time, the presence of typical macrophage-like type A cells in the lining layer was confirmed by immunoelectron microscopy. The slender processes of Hsp25-positive cells showed a continuous covering with the synovial surface at P7, followed by a drastic increase in the Hsp25-positive cells at P15 and later, when active jaw movement occurred. These findings suggested that the arrangement and morphological maturation of type B cells are closely related to the formation of the articular cavity in the embryonic period and the commencement of active jaw movement after birth, respectively.
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