RESUMO
Growing data have indicated that the miR-17-92 cluster is implicated in inflammatory response and rheumatoid arthritis (RA). This study was aimed to investigate the effects of miR-92a on the proliferation and migration of rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs). Our results showed that miR-92a was significantly down-regulated in RA synovial tissue and RA-FLSs, whereas the protein level of AKT2 is increased. Restoration of miR-92a suppressed the proliferation and migration of RA-FLSs. Down-regulation of miR-92a promotes proliferation and migration of normal human FLSs. Dual luciferase reporter gene assay showed that miR-92a could specifically bind with the 30UTR of AKT2 and significantly repressed the luciferase activity. Down-regulation or up-regulation of miR-92a significantly increased or decreased the protein and phosphorylation levels of AKT2. siRNA-mediated down-regulation of AKT2 significantly prevented cell proliferation and migration of RA-FLSs, which were similar to the effects induced by overexpression of miR-92a. Moreover, AKT2 overexpression rescued miR-92a-mediated suppressive effect on proliferation and migration of RA-FLS. Thus, miR-92a could inhibit the proliferation and migration of RA-FLSs through regulation of AKT2 expression.
Assuntos
Artrite Reumatoide/genética , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Sinoviócitos/metabolismo , Regiões 3' não Traduzidas , Adulto , Idoso , Apoptose , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Sequência de Bases , Sítios de Ligação , Estudos de Casos e Controles , Movimento Celular , Proliferação de Células , Feminino , Regulação da Expressão Gênica , Genes Reporter , Humanos , Luciferases/genética , Luciferases/metabolismo , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Cultura Primária de Células , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia , Sinoviócitos/patologiaRESUMO
Osteoarthritis is a type of joint disease that may lead to other joint diseases. Previous research has demonstrated that tumor necrosis factor (TNF)α is associated with osteoarthritis activity and pathology. The possible mechanisms of the TNFαmediated signaling pathway have not been clearly elaborated in synovial fibroblasts. The present study aimed to investigate the potential mechanisms of TNFα in a mouse model of iodoacetateinduced osteoarthritis. Reverse transcriptionquantitative polymerase chain reaction, ELISA, western blotting and immunohistochemistry were performed to evaluate the role of TNFα in the progression of osteoarthritis. The results revealed that the serum levels of TNFα, interleukin (IL)1ß, IL4 and IL6 were significantly upregulated in a mouse model of iodoacetateinduced osteoarthritis compared with healthy mice (P<0.01). TNFα, IL1ß, IL4 and IL6 mRNA and protein levels were also significantly upregulated in synovial fibroblasts in the experimental mice (P<0.01). It was demonstrated that TNFα increased proinflammation factors matrix metalloproteinase (MMP)3, MMP9, nuclear factor (NF)κB and receptor activator of NFκB ligand (RANKL) in synovial fibroblasts. It was also observed that the tolllike receptor (TLR)3 was significantly upregulated and extracellular signalregulated kinase (ERK) and protein kinase B (AKT) were significantly downregulated in synovial fibroblasts in osteoarthritis mice (P<0.01). An in vitro assay demonstrated that TNFα inhibitor decreased mRNA and protein levels of IL1ß, IL4 and IL6 in synovial fibroblasts. The knockdown of TLR3 abolished the TNFα upregulated mRNA and protein levels of IL1ß, IL4 and IL6 in synovial fibroblasts. In addition, the knockdown of TLR3 also reversed TNFαupregulated ERK and AKT expression in synovial fibroblasts. In vivo assays demonstrated that TNFα inhibitor significantly decreased the deposition of IL1ß, IL4 and IL6 as well as bone destruction and significantly increased the body weight and osteoarthritis score for osteoarthritic mice (P<0.01). TNFα inhibitor decreased TLR3 and significantly increased the expression and phosphorylation of ERK and AKT in articular cartilage (P<0.01). In conclusion the results of the present study indicate that TNFα serves an essential role in synovial fibroblasts in osteoarthritis, suggesting that inhibition of TNFα may decrease inflammation via the TLR3mediated ERK/AKT signaling pathway in a mouse model of monosodium iodoacetateinduced osteoarthritis.
Assuntos
Artrite Reumatoide/genética , Artrite Reumatoide/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Fibroblastos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Receptor 3 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Animais , Artrite Reumatoide/patologia , Osso e Ossos/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , RNA Interferente Pequeno/genética , Receptor 3 Toll-Like/genéticaRESUMO
OBJECTIVE: To study the clinical efficacy of double bundle posterior cruciate ligament (PCL) reconstruction with remnant preservation. METHODS: From January 2007 to November 2011, 50 patients with PCL rupture met the inclusion criteria were divided into two groups: remnant preservation group (RP group) and remnant resection group (RR group). There were 19 males and 7 females in the RP group, ranging in age from 18 to 55 years, with a mean of (32.250 +/- 11.085) years old. The duration from injury to operation ranged from 2 to 66 months, with an average of (17.481 +/- 3.568) months. Among the RR group, 17 patients were male and 7 patients were female, ranging in age from 20 to 54 years old, with an average of (31.458 +/- 9.569) years. The duration from injury to operation ranged from 3 to 72 months, with a mean of (19.354 +/- 3.950) months. The patients in both groups suffered from instability of knee joint, got a positive result of posterior drawer test. In the RP group, the intercondylar notch remnant fiber, scar tissue and synovial were preserved in operation, only the free ligament in the intercondylar notch was resected. In the RR group, the remnant fiber, scar tissue and synovial tissue of adhesive parts were resected. In both groups, autologous semitendinosus and gracilis tendon double-bundle PCL reconstruction were carried out, the tibia was fixed with an absorbable interference screw with post-tie fixation, and the femur side was compositely fixed with absorbable interference screws and suspending fixation. Each patient received both subjective assessment (IKDC subjective evaluation, Lysholm scoring and Cincinnati rating) and objective clinical assessment (IKDC objective evaluation and Kneelax 3 tibia backward measurement) before operation and two years after operation. RESULTS: IKDC subjective evaluation: 92.167 +/- 4.177 in the RP group,which was higher than 87.542 +/- 5.687 in the RR group (P = 0.010). Lysholm scores: 90.917 +/- 4.413 in the RP group, which was higher than 87.083 +/- 5.149 in the RR group (P = 0.027). Cincinnati knee scores: 92.125 +/- 4.003 in the RP group, which was higher than 87.791 +/- 6.665 in the RR group (P = 0.027). IKDC objective evaluation:no significant statistical differences between RP group and RR group. Kneelax 3 assessment : tibia backward test with Kneelax 3 under 132 N showed no significant statistical difference between RP group and RR group, which were (3.958 +/- 0.693) mm and (4.029 +/- 0.846) mm respectively (P = 0.795). CONCLUSION: The study shows a significant advantage of remnant fiber preservation than remnant fiber resection in double-bundle PCL construction in terms of subjective knee function recovery after operation. There is no significant difference in postoperative knee stability.
Assuntos
Articulação do Joelho/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Ligamento Cruzado Posterior/cirurgia , Adolescente , Adulto , Artroscopia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
Our aim was to compare hip arthroplasty with internal screw fixation in the repair of intertrochanteric fractures in elderly patients with osteoporosis. Of 112 included patient, 70 (81.81 ± 4.88 years) received hip arthroplasty with a prosthesis specially designed for intertrochanteric fractures, and 42 (83.46 ± 5.11 years) underwent plate-screw fixation. The hip arthroplasty group had significantly longer operation time, intraoperative blood loss, and total volume of blood transfused but had shorter time to beginning weight-bearing (5.94 ± 2.76 vs 23.68 ± 22.01 days) and higher postoperative Harris hip score (91.37 ± 4.80 vs 86.14 ± 5.46). In the arthroplasty group, there were 2 dislocations; and in the plate-screw fixation group, there were 5 internal fixation failures. Hip arthroplasty is preferable to internal fixation in elderly patients (age >80 years) with osteoporosis.
Assuntos
Artroplastia de Quadril/instrumentação , Artroplastia de Quadril/métodos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fraturas do Quadril/cirurgia , Prótese de Quadril , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Placas Ósseas , Parafusos Ósseos , Feminino , Fraturas do Quadril/etiologia , Humanos , Masculino , Osteoporose/complicações , Desenho de Prótese , Estudos Retrospectivos , Falha de Tratamento , Resultado do Tratamento , Suporte de CargaRESUMO
OBJECTIVE: To evaluate the effectiveness of open reduction and internal fixation and repair of palmar ligment in treating trans-scaphoid perilunate dislocation. METHODS: From June 1995 to June 2001,14 patients with trans-scaphoid perilunate dislocation were treated with open reduction and internal fixation and repair of palmar ligment. Among them,there were 13 males and 1 female,the ranging in age from 21 to 38 years,averaged 25.4 years. All patients were posterior dislocation and all operations were performed within 2 weeks after injury. RESULTS: All patients were followed up from 24 to 60 months with an average of 28.3 months. Thirteen scaphoid fractures were primary healed and functions of wrist joint were good. Bone disunion was found in 1 case and part functions of wrist joint were limited. No found necrosis of lunate and scaphoid. According to clinical scoring system of Cooney, 9 case got excellent results, 3 good, 1 fair and 1 poor. CONCLUSION: Open reduction and internal fixation and repair of palmar ligament is effective in treating trans-scaphoid perilunate dislocation,which can early provide steady fixation for scaphoid,and profit to recover blood supply of lunatum and subterminal scaphoid.