RESUMO
Angiogenesis is physiologically essential for embryogenesis and development and reinitiated in adult animals during tissue growth and repair. Forming new vessels from the walls of existing vessels occurs as a multistep process coordinated by sprouting, branching, and a new lumenized network formation. However, little is known regarding the molecular mechanisms that form new tubular structures, especially molecules regulating the proper network density of newly formed capillaries. This study conducted microarray analyses in human primary microvascular endothelial cells (HMVECs) plated on Matrigel. The RAPGEF4 gene that encodes exchange proteins directly activated by cAMP 2 (EPAC2) proteins was increased in Matrigel-driven tubulogenesis. Tube formation was suppressed by the overexpression of EPAC2 and enhanced by EPAC2 knockdown in endothelial cells. Endothelial cell morphology was changed to round cell morphology by EPAC2 overexpression, while EPAC2 knockdown showed an elongated cell shape with filopodia-like protrusions. Furthermore, increased EPAC2 inhibited endothelial cell migration, and ablation of EPAC2 inversely enhanced cell mobility. These results suggest that EPAC2 affects the morphology and migration of microvascular endothelial cells and is involved in the termination and proper network formation of vascular tubes.
Assuntos
Células Endoteliais/efeitos dos fármacos , Endotélio Vascular/crescimento & desenvolvimento , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Morfogênese , 8-Bromo Monofosfato de Adenosina Cíclica/análogos & derivados , 8-Bromo Monofosfato de Adenosina Cíclica/farmacologia , Movimento Celular , Forma Celular , Células Cultivadas , Colágeno , Combinação de Medicamentos , Fatores de Troca do Nucleotídeo Guanina/genética , Células HEK293 , Humanos , Laminina , Proteoglicanas , PseudópodesRESUMO
Soluble fms-like tyrosine kinase-1 (sFlt-1) functions as a potent inhibitor of angiogenesis by trapping vascular endothelial growth factor (VEGF). However, the precise regulatory mechanism of sFlt-1 production is unknown. Here, we report that vascular sFlt-1 production is regulated by heterogeneous nuclear ribonucleoprotein D (hnRNP D) and arginine methylation. We showed that hnRNP D bound to Flt-1 pre-mRNA and that hnRNP D overexpression decreased sFlt-1 mRNA in human microvascular endothelial cells (HMVECs). In contrast, the reduction of hnRNP D levels induced an increase in sFlt-1 production. Overexpression of an hnRNP D mutant in which the arginine residue of the known arginine methylation motif (arginine-glycine-glycine; RGG) was replaced with alanine did not reduce the level of soluble-form RNA produced from the Flt-1 minigene. Moreover, we demonstrated that overexpression of arginine methyltransferase decreased the soluble-form RNA level, whereas overexpression of arginine demethylase and addition of methyltransferase inhibitors increased sFlt-1 mRNA levels. These findings indicate that hnRNP D and arginine methylation play important roles in the regulation of Flt-1 mRNA alternative polyadenylation.
Assuntos
Arginina/metabolismo , Regulação da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo D/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Linhagem Celular , Células Endoteliais/metabolismo , Ribonucleoproteína Nuclear Heterogênea D0 , Humanos , Metilação , Microvasos/citologia , Poliadenilação , RNA Mensageiro/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismoRESUMO
Family with sequence similarity 107 (FAM107) proteins consist of two subtypes, FAM107A and FAM107B in mammals, possessing a conserved N-terminal domain of unknown function. Recently we found that FAM107B, an 18 kDa nuclear protein, is expressed in a broad range of tissues and is downregulated in gastrointestinal cancer. Because FAM107B expression is amplified by heat-shock stimulation, we designated it heat shock-inducible tumor small protein (HITS). Although data related to FAM107A as a candidate tumor suppressor have been accumulated, little biological information is available for HITS. In the present study, we examined HITS expression using immunohistochemistry with tissue microarrays and performed detailed statistical analyses. By screening a high-density multiple organ tumor and normal tissue microarray, HITS expression was decreased in tumor tissues of the breast, thyroid, testis and uterine cervix as well as the stomach and colon. Further analysis of tissue microarrays of individual organs showed that loss of HITS expression in cancer tissues was statistically significant and commonly observed in distinct organs in a histological type-specific manner. The HITS expression intensity was inversely correlated with the primary tumor size in breast and thyroid cancers. In addition, effects of tetracycline-inducible HITS expression on tumor growth were investigated in vivo. Forced expression of HITS inhibited tumor xenograft proliferation, compared with the mock-treated tumor xenograft model. These results show that loss of HITS expression is a common phenomenon observed in cancers of distinct organs and involved in tumor development and proliferation.
Assuntos
Carcinogênese/genética , Hidrolases/genética , Neoplasias/genética , Análise Serial de Tecidos , Animais , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Hidrolases/biossíntese , Neoplasias/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
sFlt-1 (soluble Flt-1) potently inhibits angiogenesis by binding extracellularly to VEGF (vascular endothelial growth factor). In the present paper, we report that hypoxia down-regulates sFlt-1 expression in HMVECs (human microvascular endothelial cells), a constituent of microvessels where angiogenesis occurs. Hypoxia (5-1% O2) increased VEGF expression in HMVECs. In contrast, the levels of sFlt-1 mRNA and protein in HMVECs decreased significantly as the O2 concentration fell, whereas mFlt-1 (membrane-bound Flt-1) mRNA and protein remained unchanged. This suggested that hypoxia selectively regulates alternative 3'-end processing of sFlt-1 pre-mRNA. We have also demonstrated that sFlt-1 overexpression in lentiviral-construct-infected HMVECs counteracted VEGF-induced endothelial cell growth. We next identified cis-elements involved in sFlt-1 mRNA processing in HMVECs using a human Flt-1 minigene and found that two non-contiguous AUUAAA sequences function as the poly(A) signal. Furthermore, we identified a cis-element in intron 13 that regulates sFlt-1 mRNA processing. Mutagenesis of the U-rich region in intron 13 caused a significant decrease in the soluble-form/membrane-form RNA ratio in the minigene-transfected HMVECs. These results suggest that decreased sFlt-1 expression due to hypoxia contributes to hypoxia-induced angiogenesis and reveals a novel mechanism regulating angiogenesis by alternative mRNA 3'-end processing.
Assuntos
Processamento Alternativo/genética , Regulação para Baixo/genética , Células Endoteliais/fisiologia , Microcirculação/genética , Processamento de Terminações 3' de RNA/genética , RNA Mensageiro/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sequência de Bases , Hipóxia Celular/genética , Células Cultivadas , Humanos , Dados de Sequência Molecular , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/biossíntese , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
PURPOSE: Epidemiological and experimental studies have revealed that exposure to ultraviolet B (UVB) light can induce cataractogenesis. The objective of this study was to determine gene expression changes in human lens epithelial cells in response to UVB exposure and identify factors that can be involved in UVB-induced cataractogenesis. METHODS: SV40 T-antigen-transformed human lens epithelial cells (SRA01/04) were irradiated at various UVB-energy levels (10-80 mJ/cm²) and checked for viability. An irradiation condition of 30 mJ/cm² was adopted for transcriptome analysis. Total RNAs isolated from UVB-exposed and unexposed cells at 12 h and 24 h after UVB exposure were examined for global gene expression changes using Affymetrix Human Gene 1.0 ST array. mRNA levels of specific genes were examined by RT-PCR and real-time PCR, and protein levels in the conditioned media were assayed by ELISA. To examine mRNA expression in human lens, primary cultured human lens epithelial (HLE) cells were prepared from surgically removed lens epithelium, and used for UVB-irradiation and expression analysis. Effects of certain gene products on SRA01/04 cell metabolism were examined using commercially available recombinant proteins. RESULTS: Expression of most the genes analyzed was essentially unchanged (between 0.5 and 2.0 fold) in UVB-irradiated cells compared to non-irradiated cells at both 12 and 24 h after UVB exposure. Sixty one and 44 genes were upregulated more than twofold by UVB exposure at 12 h and 24 h, respectively. Emphasis was placed on genes encoding extracellular proteins, especially growth factors and cytokines. A total of 18 secreted protein genes were upregulated more than twofold at either or both time points. Amphiregulin (AREG) and growth differentiation factor 15 (GDF15) were chosen because of their higher upregulation and novelty, and their upregulation was confirmed in SRA01/04 cells using RT-PCR and real-time PCR analysis. AREG and GDF15 protein levels in conditioned media significantly increased at all UVB-energy points at 24 h, while they were scarcely detectable at 12 h. AREG and GDF15 mRNA levels were also significantly upregulated in UVB-irradiated primary cultured HLE cells compared with the corresponding control culture. AREG significantly stimulated ³H-thymidine and ³H-leucine uptake in SRA01/04 cells as did a positive control epidermal growth factor (EGF). Recombinant GDF15 did not stimulate ³H-thymidine incorporation at any concentration tested, but significantly stimulated ³H-leucine uptake. RT-PCR analysis demonstrated that primary cultured HLE and SRA01/04 cells expressed not only epidermal growth factor receptor (EGFR) mRNA but also transforming growth factor ß receptors (TGFBR1 and TGFBR2) mRNAs. CONCLUSIONS: These results indicate that AREG and GDF15 produced in response to UVB exposure can affect the growth and protein synthesis of lens epithelial cells, suggesting that they have autocrine and paracrine roles related to pathological changes of lens tissue during long-term UVB exposure.
Assuntos
Catarata/metabolismo , Células Epiteliais/citologia , Glicoproteínas/biossíntese , Fator 15 de Diferenciação de Crescimento/biossíntese , Peptídeos e Proteínas de Sinalização Intercelular/biossíntese , Cristalino/citologia , Raios Ultravioleta , Anfirregulina , Sobrevivência Celular , Células Cultivadas , Primers do DNA/genética , Família de Proteínas EGF , Ensaio de Imunoadsorção Enzimática/métodos , Células Epiteliais/efeitos da radiação , Regulação da Expressão Gênica , Glicoproteínas/genética , Fator 15 de Diferenciação de Crescimento/genética , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/genética , Cristalino/efeitos da radiação , Análise de Sequência com Séries de Oligonucleotídeos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fatores de TempoRESUMO
The Family with sequence similarity 107 (FAM107) possesses an N-terminal domain of unknown function (DUF1151) that is highly conserved beyond species. In human, FAM107A termed TU3A/DRR1 has been reported as a candidate tumor suppressor gene which expression is downregulated in several types of cancer, however no studies have investigated the other family protein, FAM107B. In the present study, we designated FAM107B as heat shock-inducible tumor small protein (HITS) and studied its expression and functional properties in cancer. HITS is an 18-kDa nuclear protein expressed in a variety of tissues including stomach, colon, lung and lymphoid organs. In human gastric and colorectal cancers and a mouse model of colon cancer, its expression in tumor cells was much lower than normal epithelial cells, while expression pattern and intensity varied among different histological types of cancer. In functional analysis in vitro, forced expression of this protein suppresses the cellular responses to growth factors. Furthermore, HITS gene carries the promoter region providing heat shock transcription factor (HSF) binding sites and amplifying the transcription of HITS by heat shock or hyperthermia treatment both in vitro and in vivo. Thus HITS would be a potential tumor suppressor gene similar to TU3A containing heat responding elements, which contrasts with previously described oncogenic activities of other heat shock proteins such as HSP70 and HSP90.
Assuntos
Proteínas de Choque Térmico/biossíntese , Resposta ao Choque Térmico , Neoplasias/metabolismo , Animais , Modelos Animais de Doenças , Células HEK293 , Células HeLa , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Humanos , Imuno-Histoquímica , Células Jurkat , Masculino , Camundongos , Camundongos Endogâmicos ICR , Neoplasias/genética , TransfecçãoRESUMO
OBJECTIVES: The objectives of this study were to assay interleukin 8 (IL-8) in synovial tissues of the temporomandibular joint (TMJ) with symptomatic internal derangement, and to assess its relationship with clinical variables. STUDY DESIGN: Forty-six joints in 44 patients were examined using an immunohistochemical technique. As controls, 8 joints in 7 subjects with habitual dislocation without pain were also examined. RESULTS: IL-8 was expressed mainly in the blood vessels beneath the lining cells in 37 of the 46 joints (80%) with internal derangement and in 2 of the 8 control joints. The percentage of IL-8-positive cells was significantly higher in the internal derangement group than in the control group (P = .004). The percentage of IL-8-positive cells showed no correlation with joint pain or number of infiltrating cells. CONCLUSIONS: IL-8 was up-regulated in inflamed synovial tissues in patients with internal derangement. Because IL-8 has no significant correlation with clinical variables, IL-8 may play a secondary role in the pathogenesis of the internal derangement of the TMJ.
Assuntos
Interleucina-8/análise , Líquido Sinovial/imunologia , Disco da Articulação Temporomandibular/imunologia , Transtornos da Articulação Temporomandibular/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Métodos Epidemiológicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disco da Articulação Temporomandibular/irrigação sanguíneaRESUMO
Our aim was to find out the extent of expression of substance P in synovial tissue from the human temporomandibular joints (TMJ) with symptomatic, non-reducing internal derangement, and to investigate the relationship between substance P and clinical findings. Fifty-four joints in 54 patients were examined immunohistochemically. Specimens of synovial tissue from 10 joints in 8 subjects with habitual dislocation of the TMJ with no pain were examined as controls. Cells that stained for substance P were found mainly among the endothelial cells in the blood vessels beneath the lining cells in synovial tissues from 47 of the 54 joints (87%) with internal derangement and from 5 of the 10 control joints. The extent score of cells that stained for substance P in joints with internal derangement was significantly higher than that in controls (p=0.02). The extent score of these cells did not correlate with pain in the joint or the degree of synovitis. These results suggest that substance P may have some roles in both the physiological and pathological conditions in patients with symptomatic internal derangement of the TMJ.
Assuntos
Substância P/biossíntese , Membrana Sinovial/metabolismo , Transtornos da Articulação Temporomandibular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/metabolismo , Estudos de Casos e Controles , Endotélio Vascular/química , Endotélio Vascular/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Luxações Articulares/metabolismo , Luxações Articulares/patologia , Masculino , Pessoa de Meia-Idade , Inflamação Neurogênica/metabolismo , Inflamação Neurogênica/patologia , Estatísticas não Paramétricas , Substância P/análise , Membrana Sinovial/química , Membrana Sinovial/patologia , Sinovite/metabolismo , Sinovite/patologia , Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE: The present study was performed to characterize the patterns of protein expression in the synovial fluid (SF) of patients with temporomandibular joint disorders (TMD) by electrophoretic fractionation. STUDY DESIGN: Samples of the SF of 26 consecutive patients consisting of 16 with closed locking (CL group) and 10 with osteoarthritis (OA group), as well as 7 asymptomatic control subjects (AS group), were analyzed in the present study. SF samples were obtained from the upper compartment of the temporomandibular joint (TMJ) and equal quantities of SF protein were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). RESULTS: The mean total protein concentrations in the SF from both of the TMD groups were higher than that in the AS group (1353 microg/mL in the CL group and 2485 microg/mL in the OA group vs 615 microg/mL in the AS group; P < .01). Moreover, the mean total SF protein concentration was higher in the OA group than in the CL group (P < .01). There was a correlation between the total protein concentration in the SF from both patient groups and the degree of expanded joint effusion (P = .003, r = 0.685). Approximately 22 different protein bands with molecular weights ranging from 14 to 700 kd were clearly discernible on electrophoresis. The relative amounts of specific proteins in the SF of the TMD group were also different from those in the AS group (P < .05). The major difference in total protein concentration appeared to be due to the increased abundance of relatively high molecular weight proteins (>140 kd) in the TMD patients as compared to the AS group. CONCLUSIONS: The SF of patients with TMD showed significant quantitative differences in total protein abundance as compared to healthy subjects. Moreover, this protein abundance was correlated strongly with the degree of expanded joint effusion. The major difference in total protein concentration appeared to be due to the increased abundance of relatively high molecular weight polypeptides in the TMD patients as compared to the healthy control subjects. These observations of changes in the pattern of protein expression may help in understanding the etiological factors involved in the pathophysiology of TMD.
Assuntos
Líquido Sinovial/química , Transtornos da Articulação Temporomandibular/metabolismo , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Eletroforese em Gel de Poliacrilamida , Feminino , Humanos , Luxações Articulares/metabolismo , Masculino , Pessoa de Meia-Idade , Peso Molecular , Osteoartrite/metabolismo , Proteínas/análise , Estatísticas não ParamétricasRESUMO
OBJECTIVE: To elucidate expression of capsaicin receptor TRPV-1 in synovial tissues of the human temporomandibular joint (TMJ) with internal derangement and discuss its relationship with joint pain. STUDY DESIGN: Fifty-four TMJs in 54 patients were examined using an immunohistochemical technique. As controls, 10 TMJs with habitual dislocation without pain were also examined. RESULTS: TRPV-1 was expressed mainly in the blood vessels beneath the lining cells in synovial tissues from 31 of the 54 joints with internal derangement and from 8 of the 10 control joints. The extent score of TRPV-1-stained cells with internal derangement was not significantly higher than that of controls. The extent score of TRPV-1 showed no correlation with joint pain. CONCLUSIONS: TRPV-1 was detected in the region of the posterior disk attachment of synovial tissues from the TMJ in patients with internal derangement and controls. TRPV-1 may play a role in maintenance of the physiologic condition of the TMJ.
Assuntos
Dor Facial/metabolismo , Membrana Sinovial/metabolismo , Canais de Cátion TRPV/biossíntese , Transtornos da Articulação Temporomandibular/metabolismo , Articulação Temporomandibular/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/metabolismo , Estudos de Casos e Controles , Feminino , Humanos , Imuno-Histoquímica , Luxações Articulares/metabolismo , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/irrigação sanguínea , Membrana Sinovial/química , Sinovite/metabolismo , Canais de Cátion TRPV/análiseRESUMO
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.
Assuntos
Líquido Sinovial/química , Transtornos da Articulação Temporomandibular/patologia , Fator A de Crescimento do Endotélio Vascular/análise , Adolescente , Adulto , Fatores Etários , Idoso , Artroscopia , Feminino , Humanos , Luxações Articulares/sangue , Luxações Articulares/patologia , Instabilidade Articular/sangue , Instabilidade Articular/patologia , Masculino , Microcirculação/patologia , Pessoa de Meia-Idade , Paracentese , Proteínas/análise , Amplitude de Movimento Articular , Membrana Sinovial/patologia , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/sangue , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
OBJECTIVE: To elucidate the expression of calcitonin gene-related peptide (CGRP) in synovial tissue taken from the human temporomandibular joint (TMJ) with internal derangement, and discuss the relationship between CGRP and joint pain. STUDY DESIGN: Using an immunohistochemical technique, 48 joints in 48 patients were examined. As controls, synovial tissue specimens from 7 joints with habitual dislocation without pain were also examined. RESULTS: In all of the internal derangement and control subjects, CGRP-positive cells were observed in the connective tissues around the blood vessels beneath the lining cells. The extent score of CGRP was significantly higher in the internal derangement group than in the control group (P=.033). There was a significant positive correlation between the extent score of CGRP and joint pain (P=.036, r=0.30). CONCLUSIONS: These results suggest that the expression of CGRP is increased in the synovial tissues from patients with internal derangement, and that CGRP seems to play an important role in the mechanism of pain production in patients with symptomatic internal derangement.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina/análise , Luxações Articulares/patologia , Membrana Sinovial/patologia , Transtornos da Articulação Temporomandibular/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artralgia/patologia , Artroscopia , Tecido Conjuntivo/patologia , Feminino , Humanos , Imuno-Histoquímica , Masculino , Microcirculação/patologia , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Membrana Sinovial/irrigação sanguínea , Sinovite/patologiaRESUMO
OBJECTIVE: We sought to elucidate the levels of fibroblast growth factor 2 (FGF-2) in synovial fluid taken from internally deranged human temporomandibular joints (TMJs) and to discuss the role of FGF-2 in the pathogenesis of internal derangement. STUDY DESIGN: Through the use of a pumping procedure, diluted synovial fluid was collected from the upper joint compartment of 22 TMJs with evidence of internal derangement (21 patients) and 8 TMJs with no such evidence (5 control subjects). Two of the control subjects were patients who had habitual dislocation, and three were healthy volunteers. The level of FGF-2 in the synovial fluid was assessed by means of an enzyme-linked immunosorbent assay. RESULTS: FGF-2 levels were at detectable levels in 15 of the 22 TMJs (68%) with internal derangement. The mean concentration of FGF-2 was 24 pg/mL. In the control group, FGF-2 levels were detectable in only 1 of 8 joints (13%), for a concentration of 3 pg/mL. The mean concentration of FGF-2 in the synovial fluid was significantly higher in the internal derangement group than in the control group (P =.02). CONCLUSIONS: FGF-2 levels are elevated in the human synovial fluid of TMJs with internal derangement.
Assuntos
Fator 2 de Crescimento de Fibroblastos/análise , Líquido Sinovial/química , Transtornos da Articulação Temporomandibular/metabolismo , Adolescente , Adulto , Idoso , Artroscopia , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Fator 2 de Crescimento de Fibroblastos/sangue , Humanos , Luxações Articulares/metabolismo , Masculino , Pessoa de Meia-Idade , Medição da Dor , Amplitude de Movimento Articular/fisiologia , Estatísticas não Paramétricas , Membrana Sinovial/patologia , Articulação Temporomandibular/metabolismo , Disco da Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE: To elucidate the correlation between the arthroscopic diagnosis of synovitis and microvessel density in synovial tissues in patients with internal derangement of the temporomandibular joint (TMJ). STUDY DESIGN: Forty-three joints in 41 patients with internal derangement were examined and biopsies taken. Microvessel density was evaluated using the immunohistochemical method for CD 34 antibody. Arthroscopically diagnosed synovitis was evaluated according to Murakami's criteria. RESULTS: In patients with internal derangement, arthroscopically diagnosed synovitis scores averaged 5.2+/-2.0, according to Murakami et al. (1991). Small to large blood vessels were observed clearly with CD 34 stain. The mean microvessel density was 22.7+/-15.6 per two high power fields (magnification x200). Synovitis scores correlated significantly with microvessel density (p=0.002, r=0.43). CONCLUSION: Synovitis evaluated using Murakami's scores correlated well with the number of blood vessels in synovial tissues in patients with internal derangement of the TMJ. This demonstrates that synovitis is linked to inflammation-related blood vessel density of the synovial tissues.
Assuntos
Artroscopia , Membrana Sinovial/irrigação sanguínea , Sinovite/diagnóstico , Transtornos da Articulação Temporomandibular/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34 , Biópsia , Feminino , Humanos , Imuno-Histoquímica , Luxações Articulares/diagnóstico , Luxações Articulares/patologia , Masculino , Microcirculação/patologia , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Disco da Articulação Temporomandibular/patologia , Transtornos da Articulação Temporomandibular/patologiaRESUMO
OBJECTIVE: The aim of this study was to elucidate the expression and localization of vascular endothelial growth factor (VEGF) in synovial tissue taken from the temporomandibular joint (TMJ) with internal derangement (ID) and discuss the role of VEGF in the pathogenesis of ID. STUDY DESIGN: Through the use of an immunohistochemical technique, 39 TMJs in 37 patients were examined. As controls, synovial tissue specimens from 6 joints in 6 patients with habitual dislocation were also examined. RESULTS: In the synovial tissue from 35 of the patients with ID, expression of VEGF was observed in the synovial lining cells, in the endothelial cells of the blood vessels, and in the fibroblasts. In contrast, expression of VEGF was found in the TMJ tissue from only 2 of the controls. The percentage of VEGF-positive cells in the ID specimens was significantly higher than that in the habitual dislocation specimens (P < .02), and the expression of VEGF significantly correlated with the arthroscopic synovitis score (P = .004). CONCLUSION: These results suggest that the expression of VEGF is upregulated and involved in the development of inflammatory changes in synovial tissues in TMJs with ID.