Vascular endothelial growth factor concentrations in synovial fluids of patients with symptomatic internal derangement of the temporomandibular joint

BACKGROUND: Vascular endothelial growth factor (VEGF) is an inducer of angiogenesis and permeability of small blood vessels. We determined the concentrations of VEGF in synovial fluid of patients with symptomatic internal derangement of the temporomandibular joint (TMJ). METHODS: Diluted synovial fluid was collected by a pumping procedure from 22 TMJs of patients with internal derangement and 10 control TMJs. VEGF concentration was determined by an enzyme-linked immunosorbent assay. RESULTS: The VEGF was detected in 14 of the 22 joints (64%) of patients with internal derangement, at a mean concentration of 67 pg/ml, but in only one control joint (12.5 pg/ml) (P = 0.004 for the difference in concentration). There was a significant correlation between VEGF concentration and total protein concentration in the synovial fluid (P = 0.002). CONCLUSIONS: The increased concentration of VEGF in patients with symptomatic internal derangement suggests that this growth factor may be involved in the pathogenesis of this condition.     

Isolation and characterization of synovial cells from the human temporomandibular joint

BACKGROUND: The synovial tissues with temporomandibular disorders (TMDs) often show chronic inflammatory changes and the synovial cells participate in the pathogenic processes of TMDs. The synovial membrane is composed of a synovial lining layer and a connective sublining layer. The synovial lining layer is made up of two kinds of cells: macrophage-like type A and fibroblastic type B cells. The aim of this study was to isolate and characterize synovial cells from the human temporomandibular joint (TMJ). METHODS: Synovial cells were isolated using an explant culture method. Then, we characterized the cultured synovial cells (SGA2 cells) using immunocytochemistry. RESULTS: SGA2 cells expressed the fibroblastic markers vimentin and prolyl 4-hydroxylase; they also expressed laminin and heat shock protein 27, all of which are markers of type B cells. However, some cells expressed the macrophage marker CD68. These CD68-positive cells simultaneously expressed laminin. CONCLUSIONS: We isolated and cultured synovial type B cells from the human TMJ, and identified the presence of intermediate type synovial lining cells, having the phenotypic properties of both type A and type B cells, among the synovial lining cells.     

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.     

Tumor necrosis factor-α increases chemokine gene expression and production in synovial fibroblasts from human temporomandibular joint

BACKGROUND: Synovitis, which is characterized by infiltration of inflammatory cells, often accompanies progression of clinical symptoms of the temporomandibular joint (TMJ). Synovial fibroblasts of the TMJ are believed to play important roles in progression of synovitis. The purpose of this study was to examine production and gene expression of chemokines by synovial fibroblasts stimulated by tumor necrosis factor-alpha (TNF-alpha). METHODS: Protein levels of chemokines were measured by enzyme-linked immunosorbent assay (ELISA). Gene expression of chemokines was analyzed by real-time polymerase chain reaction (PCR). RESULTS: Production of interleukin (IL)-8, growth-related oncogene (GRO)-alpha, monocyte chemoattractant protein (MCP)-1, and regulated upon activation normal T-cell expressed and secreted (RANTES) protein by synovial fibroblasts was increased by TNF-alpha. In contrast, stromal cell-derived factor (SDF)-1alpha, macrophage inflammatory protein (MIP)-1alpha and -1beta were not detectable in conditioned media of synovial fibroblasts, with or without TNF-alpha treatment. Increases in gene expression of IL-8, GRO-alpha, MCP-1, and RANTES in response to TNF-alpha treatment were detected. CONCLUSIONS: Increased protein production and gene expression of chemokines by synovial fibroblasts in response to TNF-alpha treatment appears to play an important role in recruitment of inflammatory cells into synovium and the progression of synovitis in the TMJ.     

Interleukin-1β increases RANTES gene expression and production in synovial fibroblasts from human temporomandibular joint

BACKGROUND: Synovial fibroblasts of temporomandibular joint (TMJ) are poorly characterized, although they have important roles in progression of temporomandibular disorders (TMD). In this study, we investigated responses of synovial fibroblasts to interleukin (IL)-1beta. METHODS: We examined gene expression profiles of synovial fibroblasts in response to IL-1beta, using Affymetrix GeneChip. Regulated upon activation normal T-cell expressed and secreted (RANTES) gene expression was confirmed by polymerase chain reaction (PCR) and real-time PCR. RANTES protein levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: The RANTES was preferentially up-regulated in synovial fibroblasts by IL-1beta. The increase in RANTES gene expression in response to IL-1beta was confirmed by PCR and real-time PCR. Protein level of RANTES in synovial fibroblasts was also increased by IL-1beta. CONCLUSIONS: The RANTES, a cc-type chemokine, has chemotactic effects on lymphocytes and monocytes. Increased gene expression and protein production of RANTES in synovial fibroblasts, in response to IL-1beta, may play an important role in recruitment of inflammatory cells into synovium and progression of synovitis in TMD.     

Enhanced expression of vascular endothelial growth factor by periodontal pathogens in gingival fibroblasts

Vascular endothelial growth factor (VEGF) has recently attracted attention as a potent inducer of vascular permeability and angiogenesis. Aberrant angiogenesis is often associated with lesion formation in chronic periodontitis. The aim of the present study was to investigate the properties of VEGF expression in human gingival fibroblasts (HGF) culture. HGF were stimulated with lipopolysaccharide (LPS), vesicle (Ve) and outer membrane protein (OMP) from Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis. HGF constitutively produced VEGF and levels were significantly enhanced (P < 0.01) by stimulation with Ve and OMP from A. actinomycetemcomitans and P. gingivalis at concentrations of 10 microg/ml or higher. On the other hand, VEGF levels were not increased by LPS stimulation. VEGF mRNA expression was also observed in Ve- and OMP-stimulated HGF. A vascular permeability enhancement (VPE) assay was performed using guinea pigs to ascertain whether supernatant from cultures of Ve- and OMP-stimulated HGF enhance vascular permeability in vivo. Supernatant from cultures of Ve- and OMP-stimulated HGF strongly induced VPE. This was markedly suppressed upon simultaneous injection of anti-VEGF polyclonal antibodies with the supernatant. Heating and protease treatment of the stimulants reduced the VEGF enhancing levels in Ve and OMP in vitro. These results suggest that Ve and OMP may be crucial heat-labile and protease-sensitive components of periodontal pathogens that enhance VEGF expression. In addition, VEGF might be associated with the etiology of periodontitis in its early stages according to neovascularization stimulated by periodontal pathogens causing swelling and edema.     

Simultaneous pigmented villonodular synovitis and synovial chondromatosis of the temporomandibular joint: case report

Pigmented villonodular synovitis and synovial chondromatosis are benign nonneoplastic proliferations originating in the synovium of unknown cause. Involvement of the temporomandibular joint (TMJ) is rare. Only 3 cases of simultaneous pigmented villonodular synovitis and synovial chondromatosis involving the TMJ have been reported. The authors report the case of a 21-year-old female with simultaneous involvement of pigmented villonodular synovitis and synovial chondromatosis in the left TMJ. Clinical examination and magnetic resonance imaging did not reveal the synovial lesions, and the diagnosis was made by arthroscopy and histological examination. The lesions were removed with arthroscopy, and the displaced disc was repositioned. The patient has been symptom-free for 13 months postoperatively.     

偏侧咀嚼对大鼠颞下颌关节滑膜VEGF表达影响的研究

目的:研究偏侧咀嚼对大鼠颞下颌关节(TMJ)滑膜血管内皮细胞生长因子(VEGF)表达的影响。方法:30只大白鼠随机分为6组,实验组间断磨除右侧上、下颌磨牙牙冠至龈下,对照组未做处理,饲养条件相同。实验1组磨除牙冠后4周末、实验2、3组磨除牙冠后10、16周末处死动物,取其双侧TMJ切片免疫组化检测。结果:实验1、2、3组双侧颞下颌关节滑膜VEGF表达较对照组增强。结论:偏侧咀嚼可引起颞下颌关节滑膜损伤,VEGF参与了其病理过程。     

Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor by periodontal fibroblasts

Agis H, Watzek G, Gruber R. Prolyl hydroxylase inhibitors increase the production of vascular endothelial growth factor by periodontal fibroblasts. J Periodont Res 2012; 47: 165–173. © 2011 John Wiley & Sons A/S Background and Objective: Pharmacological inhibitors of prolyl hydroxylases (PHDs) can induce a proangiogenic response that favors wound healing and bone regeneration. However, the response of periodontal cells to PHD inhibitors is unknown. Material and Methods: To determine the effects of PHD inhibitors on periodontal cells, we exposed human fibroblasts from the gingiva and the periodontal ligament to dimethyloxallyl glycine, desferrioxamine, l ‐mimosine and CoCl₂. Viability, proliferation, and protein synthesis were assessed by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT), [³H]thymidine, and [³H]leucine incorporation, respectively. The levels of Ki67, hypoxia‐inducible factor 1α (HIF‐1α), p27, phosphorylated c‐Jun N‐terminal kinase (JNK) and phosphorylated p38 were determined by immunohistochemistry and western blotting. Vascular endothelial growth factor (VEGF) mRNA levels were measured by quantitative PCR. Protein levels of VEGF and interleukin (IL)‐6 were evaluated by immunoassays. Results: We found that PHD inhibitors, while leaving cell viability unchanged, reduced proliferation and protein synthesis. This was paralleled by decreased Ki67 levels and increased p27 levels, suggesting that PHD inhibitors provoke growth arrest. Independently from this response, PHD inhibitors stabilized HIF‐1α and increased the production of VEGF. This increase of VEGF was observed in the presence of proinflammatory IL‐1 and pharmacological inhibitors of JNK and p38 signaling. Moreover, PHD inhibitors did not modulate expression of IL‐6 and the phosphorylation of JNK and p38. Conclusion: These results suggest that PHD inhibitors enhance the production of VEGF in periodontal fibroblasts, even in the presence of proinflammatory IL‐1. The data further suggest that PHD inhibitors do not provoke a significant proinflammatory or anti‐inflammatory response in this in vitro setting.     

偏侧咀嚼对大鼠TMJ滑膜iNOS表达影响的研究

目的：研究偏侧咀嚼对大鼠颞下颌关节（TMJ）滑膜诱导型一氧化氮合酶（inducible nitric oxide synthase,iNOS）表达的影响。方法：30只大白鼠随机分为6组,实验1.2.3组,对照1.2.3组,每组5只。实验组间断磨除右侧上、下颌磨牙牙冠至龈下,对照组不做处理,饲养条件相同。分别于实验后4周、10周、16周末各处死实验组与对照组各1组动物,取其双侧TMJ切片免疫组化实验,与对照组比较。结果：实验1、2、3组双侧颞下颌关节滑膜iNOS表达增强。结论：偏侧咀嚼可引起颞下颌关节滑膜损伤,iNOS参与了其病理过程。     

血管内皮生长因子在人牙髓中的表达

目的：研究血管内皮生长因子（ vascular endothelial growth factor VEGF） 在正常、深龋或炎症牙髓中的表达及其意义。方法：采用免疫组化SABC法，对牙髓中的VEGF的表达进行组织学定位，并通过Image pro-plus 5.1图像分析软件对成牙本质细胞和牙髓成纤维细胞中VEGF染色进行平均光密度值（optical density OD）测定。利用SPSS13．0统计软件对各组数据进行单因素方差分析或秩和检验。结果：人牙髓中，VEGF主要表达在血管内皮细胞、成牙本质样细胞和牙髓成纤维细胞的胞浆中。正常组成牙本质细胞的VEGF表达较其它两组弱（P〈0.01）。与正常组相比，牙髓成纤维细胞中VEGF的表达在深龋组明显增强（P〈0．05），而在炎症组明显减弱（P〈0．05）。此外，VEGF在炎症组的某些炎细胞如中性粒细胞、浆细胞的胞浆中也有表达。结论：VEGF在龋病、牙髓炎中的变化可能与牙髓炎的发生、炎症发展有关，并且可能参与了成牙本质样细胞对牙髓损伤的修复过程。     

Up-regulation of interleukin-6 and vascular endothelial growth factor-A in the synovial fluid of temporomandibular joints affected by synovial chondromatosis

Our aim was to explore important inflammatory mediators for synovial chondromatosis in the temporomandibular joints (TMJs) by analysing synovial fluid. Samples were collected from 10 patients with unilateral synovial chondromatosis of the TMJ. Control samples were obtained from 11 subjects with no symptoms in the TMJ. Concentrations of aggrecan, interleukin (IL)-2, IL-4, IL-5, IL-6, IL-8 (CXCL8), IL-10, interferon (IFN)-γ, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF)-A were measured in the samples of synovial fluid, and the results in the two groups compared. The tissues from the affected TMJ were examined histologically and immunohistochemically. Of the proteins evaluated, the concentrations of aggrecan, IL-6, and VEGF-A were significantly higher in the group with synovial chondromatosis. The immunohistochemical analysis showed that the synovial cells around the osteocartilaginous nodules were vigorously expressing VEGF-A.     

A case of synovial chondromatosis of the temporomandibular joint secondary to preauricular trauma

Synovial chondromatosis is a rare benign arthropathy characterized by chondrometaplasia of the synovial membrane, particularly in the temporomandibular joint (TMJ). The purpose of this article is to describe an uncommon case of synovial chondromatosis arising from the inferior joint space of the TMJ with an enlarged condyle secondary to preauricular trauma in a 44-year-old healthy male. The possible role of a traumatic event in the etiology, the usefulness of the combined performance of CT and MRI examinations for preoperative diagnosis and current treatment are discussed.     

Arthroscopically guided removal of large solitary synovial chondromatosis from the temporomandibular joint

Synovial chondromatosis of the joint is a rare benign condition characterized by the formation of metaplastic cartilage in the synovium of the joint resulting in numerous attached and unattached osteocartilagenous bodies. Involvement of the temporomandibular joint (TMJ) is uncommon. Arthrotomy is usually applied to remove the larger particles and the affected synovial tissues. The authors report the case of a 48-year-old female with a large solitary synovial chondroma in the left TMJ. The larger mass was removed successfully via an additional incision in the anterior wall of external auditory meatus under the guidance of arthroscopy. The patient has been symptom-free for 5 years postoperatively.     

Synovial entrapment in alloplastic temporomandibular joint replacement

Complications of alloplastic temporomandibular joint (TMJ) prostheses can lead to stress and anxiety for the patient and the surgical team, and prosthesis substitution is sometimes required. The aim of this case report is to describe the surgical finding of synovial entrapment with interposed fibrosis in a postoperative alloplastic TMJ revision, managed effectively with adequate surgical debridement. The authors believe that synovial entrapment needs to be considered as a possible postoperative complication of total joint replacement when no clear symptoms of infection, metal hypersensitivity, osteolysis, or heterotopic bone formation are present. The implications of synovial entrapment in TMJ alloplastic replacement remains relatively unpredictable and poorly understood.     

Aggrecanase analysis of synovial fluid of temporomandibular joint disorders

OBJECTIVES: To determine whether or not aggrecanase in synovial fluid can be used as a biochemical marker in the diagnosis of temporomandibular joint disorder (TMJD). MATERIALS AND METHODS: Forty-four samples of synovial fluid were obtained from 35 patients with internal derangement or osteoarthritis and 15 control samples from 10 asymptomatic volunteers. Aggrecanase in the synovial fluid was examined by immunoblotting. RESULT: The incidence of aggrecanase expression in TMJD group were significantly higher than that in the normal control group (P < 0.05). Those with severe OA and anterior disc displacement without reduction showed significantly high expression of aggrecanase compared with other disease subgroups (P < 0.05). CONCLUSION: These findings suggested that aggrecanase could be a potential biochemical marker for cartilage degeneration in the TMJD.     

Expression of chemerin in the synovial fluid of patients with temporomandibular joint disorders

The synovial membrane and fluid are significantly involved in the pathogenesis of temporomandibular joint (TMJ) disorders. This study aimed to investigate the relation between levels of chemerin in the synovial fluid (SF) of patients with TMJ disorder and their relationship. Sixty samples of SF were obtained from patients with an internal derangement (ID) or osteoarthritis (OA). Chemerin in the SF was examined by enzyme‐linked immunosorbent assay (ELISA). The results showed greater levels of chemerin in the SF of patients with OA than ID. While chemerin levels were positively correlated with pain scores, they were inversely correlated with MMO. Chemerin levels increased progressively as the disorder stage became more severe. The findings of this study suggest that chemerin in SF may play role as a predisposing factor and may represent a novel potential prognostic biochemical marker in the pathogenesis of TMJ disorders.