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BACKGROUND: Many factors affect the prognosis of hip fractures in the elderly. Some studies have suggested a direct or indirect association among serum lipid levels, osteoporosis, and hip fracture risk. LDL levels were found to have a statistically significant nonlinear U-shaped relationship with hip fracture risk. However, the relationship between serum LDL levels and the prognosis of patients with hip fractures remains unclear. Therefore, in this study, we assessed the influence of serum LDL levels on patient mortality over a long-term follow-up period. METHODS: Elderly patients with hip fractures were screened between January 2015 and September 2019, and their demographic and clinical characteristics were collected. Linear and nonlinear multivariate Cox regression models were used to identify the association between LDL levels and mortality. Analyses were performed using Empower Stats and R software. RESULTS: Overall, 339 patients with a mean follow-up period of 34.17 months were included in this study. Ninety-nine patients (29.20%) died due to all-cause mortality. Linear multivariate Cox regression models showed that LDL levels were associated with mortality (HR = 0.69, 95%CI: 0.53, 0.91, p = 0.0085) after adjusting for confounding factors. However, the linear association was unstable, and nonlinearity was identified. An LDL concentration of 2.31 mmol/L was defined as the inflection point for prediction. A LDL level < 2.31 mmol/L was associated with mortality (HR = 0.42, 95%CI: 0.25, 0.69, p = 0.0006), whereas LDL > 2.31 mmol/L was not a risk factor for mortality (HR = 1.06, 95%CI: 0.70, 1.63, p = 0.7722). CONCLUSIONS: The preoperative LDL level was nonlinearly associated with mortality in elderly patients with hip fractures, and the LDL level was a risk indicator of mortality. Furthermore, 2.31 mmol/L could be considered a predictor cut-off for risk.
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PURPOSE: Acute septic arthritis after arthroscopic posterior cruciate ligament (PCL) reconstruction is a rare but severe complication. Optimal management has not been established. The purposes of this study were to analyze clinical findings and to retrospectively evaluate the graft-retaining treatment regimen. METHODS: From 2010 to 2021, a total of 1561 primary PCL reconstructions were performed at our institution. Seven patients with septic arthritis were identified and retrospectively analyzed with regard to incidence, clinical manifestations, treatment, postoperative clinical course and follow-up results. RESULTS: The mean interval from PCL reconstruction to the onset of symptoms was 11.0 ± 4.0 days. Staphylococcus aureus was the most commonly found pathogen. Eradication was achieved in all patients after a mean of 1.1 ± 0.4 procedures, with graft retention in all patients. The mean duration of antibiotic treatment was 5.7 ± 1.5 weeks. At the last follow-up, there was no recurrence, graft insufficiency or osteoarthritis. CONCLUSION: Arthroscopic graft-retaining treatment combined with individual antibiotic therapy, eradication and good to excellent functional results can be achieved, which might encourage surgeons to try to retain the graft as much as possible. LEVEL OF EVIDENCE: Level IV.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Artritis Infecciosa , Reconstrucción del Ligamento Cruzado Posterior , Ligamento Cruzado Posterior , Humanos , Estudios Retrospectivos , Reconstrucción del Ligamento Cruzado Posterior/efectos adversos , Protocolos Clínicos , Reconstrucción del Ligamento Cruzado Anterior/métodos , Artritis Infecciosa/tratamiento farmacológico , Artritis Infecciosa/cirugía , Artritis Infecciosa/etiología , Ligamento Cruzado Posterior/cirugía , Lesiones del Ligamento Cruzado Anterior/cirugía , Artroscopía/efectos adversosRESUMEN
PURPOSE: To review a series of adolescent patients with anterior cruciate ligament (ACL) injuries surgically treated with robot-assisted all-epiphyseal ACL reconstruction (ACLR), and to compare with the traditional freehand group. METHODS: This retrospective clinical study included 16 patients with ACL injuries who underwent ACLR by robot-assisted technique or traditional freehand method from June 2018 to March 2020. All patients were divided into the robot-assisted group (6 patients) or the traditional surgery group (10 patients). The number of intra-operative fluoroscopies, operation time, accuracy of bone tunnel insertions, International Knee Documentation Committee (IKDC) subjective score and ligament laxity testing were recorded in the two groups. RESULTS: All patients returned for follow-up, at a mean of 31.6 ± 4.5 months after surgery. The average age of the robot-assisted group was 12.2 ± 1.3 years. The number of intra-operative fluoroscopies was 10.9 ± 2.8 in the traditional freehand group, whereas it was only 3.0 ± 0.6 in the robot-assisted group, which was significantly lower (P < 0.05). The operative time in the robot-assisted group was shorter than that in the traditional freehand group (87 ± 10.7 min vs. 126 ± 12.1 min, P < 0.05). The distance between the center of actual insertion and the center of the idea insertion on both femoral and tibial intra-articular bone tunnel were 1.5 ± 0.3 mm and 1.6 ± 0.3 mm for the robot-assisted group and 2.7 mm ± 0.4 mm and 2.4 ± 0.4 mm for the traditional freehand group (P < 0.05). There were no significant differences between the two groups in function recovery at the last follow-up. CONCLUSIONS: All-epiphyseal ACLR is a technically demanding procedure with a small margin of error. Robot-assisted treatment of ACL injuries in skeletally immature patients is more accurate than traditional freehand method, with shorter operation time and fewer intra-operative fluoroscopies.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Robótica , Adolescente , Humanos , Niño , Lesiones del Ligamento Cruzado Anterior/cirugía , Estudios Retrospectivos , Ligamento Cruzado Anterior/cirugía , Articulación de la Rodilla/cirugía , Reconstrucción del Ligamento Cruzado Anterior/métodos , Resultado del TratamientoRESUMEN
INTRODUCTION: The analgesic comparison between perineural and intravenous dexamethasone on interscalene block for pain management after shoulder arthroscopy remains controversial. We conduct this meta-analysis to explore the influence of perineural versus intravenous dexamethasone on interscalene block for pain control after shoulder arthroscopy. METHODS: We have searched PubMed, Embase, Web of science, EBSCO and Cochrane library databases through April 2021 and included randomized controlled trials (RCTs) assessing the effect of perineural and intravenous dexamethasone on interscalene block in patients with shoulder arthroscopy. RESULTS: Five RCTs were included in the meta-analysis. Overall, compared with intravenous dexamethasone for shoulder arthroscopy, perineural dexamethasone led to similar block duration (SMD = 0.12; 95% CI - 0.12 to 0.35; P = 0.33), pain scores at 12 h (SMD = - 0.67; 95% CI - 1.48 to 0.15; P = 0.11), pain scores at 24 h (SMD = - 0.33; 95% CI - 0.79 to 0.14; P = 0.17), opioid consumption (SMD = 0.01; 95% CI - 0.18 to 0.19; P = 0.95) and incidence of nausea/vomiting (OR = 0.74; 95% CI 0.38-1.44; P = 0.38). CONCLUSIONS: Perineural and intravenous dexamethasone demonstrated comparable pain relief after shoulder arthroscopy.
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Analgésicos/administración & dosificación , Artroscopía/efectos adversos , Dexametasona/administración & dosificación , Dolor Postoperatorio/tratamiento farmacológico , Hombro/cirugía , Administración Intravenosa , Analgésicos/uso terapéutico , Dexametasona/uso terapéutico , Humanos , Manejo del Dolor , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Osteoarthritis (OA) is a proverbial inflammatory degenerative joint disease associated with the acceleration of the aging process and is characterized by chondrocyte injury and articular cartilage degradation. Dual-specificity phosphatase 14 (Dusp14), a common member of the DUSP family, has been implicated in multiple inflammatory diseases and bone loss. Nevertheless, the function of DUSP14 in OA remains unclear. In the present study, down-regulation of DUSP14 was corroborated in anterior cruciate ligament transection (ACLT)-induced OA rats and interleukin-1ß (IL-1ß)-stimulated chondrocytes. Additionally, the gain of DUSP14 reversed IL-1ß-induced inhibition of chondrocyte viability but attenuated cell apoptosis. Concomitantly, DUSP14 overexpression muted IL-1ß-induced release of pro-inflammatory mediators NO and prostaglandin E2 (PGE2), as well as pro-inflammatory cytokine levels (IL-6 and TNF-α). Furthermore, up-regulation of DUSP14 overturned the effects of IL-1ß on the inhibition of collagen II and aggrecan expression, and enhancement of A Disintegrin and Metalloproteinase with Thrombospondin Motifs 5 (ADAMTS5) and matrix metalloproteinases (MMPs; MMP3 and MMP-13). Mechanistically, DUSP14 elevation increased the p-Adenosine 5'-monophosphate-activated protein activated protein kinase(AMPK), inhibitor of NF-κB (IκB) expression and decreased p-p65 NF-κB expression, indicating that DUSP14 might restore the AMPK-IκB pathway to restrain NF-κB signaling under IL-1ß exposure. Notably, blockage of AMPK signaling muted the protective efficacy of DUSP14 elevation against IL-1ß-induced inflammatory injury and metabolism disturbance in chondrocytes. Interestingly, histological evaluation substantiated that DUSP14 injection alleviated cartilage degradation in OA rats. Together, DUSP14 may ameliorate OA progression by affecting chondrocyte injury, inflammatory response and cartilage metabolism homeostasis, implying a promising therapeutic strategy against OA.
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Condrocitos/metabolismo , Fosfatasas de Especificidad Dual , Fosfatasas de la Proteína Quinasa Activada por Mitógenos , Osteoartritis , Animales , Células Cultivadas , Citocinas/metabolismo , Progresión de la Enfermedad , Fosfatasas de Especificidad Dual/genética , Fosfatasas de Especificidad Dual/metabolismo , Homeostasis , Inflamación/metabolismo , Masculino , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/genética , Fosfatasas de la Proteína Quinasa Activada por Mitógenos/metabolismo , Osteoartritis/metabolismo , Osteoartritis/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
AIMS: Osteoarthritis (OA) is characterized by persistent destruction of articular cartilage. It has been found that microRNAs (miRNAs) are closely related to the occurrence and development of OA. The purpose of the present study was to investigate the mechanism of miR-486 in the development and progression of OA. METHODS: The expression levels of miR-486 in cartilage were determined by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of collagen, type II, alpha 1 (COL2A1), aggrecan (ACAN), matrix metalloproteinase (MMP)-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS4) in SW1353 cells at both messenger RNA (mRNA) and protein levels was determined by qRT-PCR, western blot, and enzyme-linked immunosorbent assay (ELISA). Double luciferase reporter gene assay, qRT-PCR, and western blot assay were used to determine whether silencing information regulator 6 (SIRT6) was involved in miR-486 induction of chondrocyte-like cells to a more catabolic phenotype. RESULTS: Compared with osteonecrosis, the expression of miR-486 was significantly upregulated in cartilage from subjects with severe OA. In addition, overexpressed miR-486 promoted a catabolic phenotype in SW1353 cells by upregulating the expressions of ADAMTS4 and MMP-13 and down-regulating the expressions of COL2A1 and ACAN. Conversely, inhibition of miR-486 had the opposite effect. Furthermore, overexpression of miR-486 significantly inhibited the expression of SIRT6, confirming that SIRT6 is a direct target of miR-486. Moreover, SW1353 cells were transfected with small interfering RNA (si)-SIRT6 and it was found that SIRT6 was involved in and inhibited miR-486-induced changes to SW1353 gene expression. CONCLUSION: Our results indicate that miR-486 promotes a catabolic phenotype in SW1353 cells in OA by targeting SIRT6. Our findings might provide a potential therapeutic target and theoretical basis for OA. Cite this article: Bone Joint Res 2021;10(7):459-466.
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CONTEXT: Osteoarthritis (OA) is one of the leading causes of disability worldwide. microRNAs (miRs) has been shown to be involved in multiple pathological processes during OA. But the possible mechanism of miR-485-3p in OA remains unclear. OBJECTIVE: This study was designed to identify the effect of miR-485-3p on OA. METHODS: miR-485-3p expression in the cartilage of OA patients and healthy controls was detected. OA cell model was established by lipopolysaccharide (LPS). miR-485-3p expression in SW1353 and CHON-001 chondrocytes treated with LPS was detected. After overexpressing miR-485-3p in chondrocytes, cell proliferation, and apoptosis were detected. Apoptosis-, extracellular matrix (ECM)-, inflammatory-, and oxidative stress-related factors were detected. The target gene of miR-485-3p was predicted by online software and verified by dual luciferase reporter gene assay. Notch2 was intervened in CHON-001 chondrocytes to detect proliferation and apoptosis. Finally, the phosphorylation of NF-κB pathway-related proteins was detected. RESULTS: miR-485-3p expression was low in OA patients and LPS-treated chondrocytes. After LPS treatment, the proliferation of SW1353 and CHON-001 chondrocytes was decreased, and apoptosis was increased. The above outcomes were reversed after overexpressing miR-485-3p. Overexpressing miR-485-3p also reduced ECM degradation, inflammation and oxidative stress in chondrocytes. miR-485-3p could target Notch2. After LPS treatment, the NF-κB pathway was activated, but miR-485-3p overexpression inhibited the pathway. Notch2 inhibition promoted proliferation and inhibited apoptosis of LPS-treated CHON-001 chondrocytes, and inhibited the NF-κB pathway. CONCLUSION: Overexpression of miR-485-3p inhibited Notch2 and the NF-κB pathway, and promoted proliferation of OA chondrocytes and inhibited apoptosis.
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Apoptosis , Proliferación Celular , Condrocitos/metabolismo , MicroARNs/metabolismo , FN-kappa B/metabolismo , Osteoartritis/metabolismo , Receptor Notch2/metabolismo , Transducción de Señal , Línea Celular , Condrocitos/patología , Femenino , Humanos , Masculino , Osteoartritis/patologíaRESUMEN
BACKGROUND: Meniscal injury is a common sports medicine condition. Magnetic resonance imaging (MRI) is widely used to effectively diagnose meniscal injury. A flag sign on MRI is usually typical of a meniscal root tear. We report the case of a "flag sign" caused by a free lateral meniscal fragment that mimicked the anterior cruciate ligament (ACL) signal on MRI. CASE PRESENTATION: This was a 21-year-old male patient who suffered a knee injury (swelling and pain) playing football. A physical examination revealed positive Lachman and lateral McMurray tests. MRI images showed an ACL injury and the flag sign, and a diagnosis of ACL tear and lateral meniscal injury was made. Arthroscopic lateral meniscal repair and ACL reconstruction were performed. Six months postoperatively, MRI showed that the injuries were well healed. In this particular case, the flag sign introduced interference to the MRI assessment of ACL injury. CONCLUSIONS: This case illustrates that clinicians should carefully identify the morphological changes in the meniscus and the relationship of the meniscus with the femoral condyle before reaching a final diagnosis.
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Lesiones del Ligamento Cruzado Anterior , Reconstrucción del Ligamento Cruzado Anterior , Lesiones de Menisco Tibial , Adulto , Lesiones del Ligamento Cruzado Anterior/diagnóstico por imagen , Lesiones del Ligamento Cruzado Anterior/cirugía , Humanos , Imagen por Resonancia Magnética , Masculino , Meniscos Tibiales/diagnóstico por imagen , Meniscos Tibiales/cirugía , Lesiones de Menisco Tibial/diagnóstico por imagen , Lesiones de Menisco Tibial/cirugía , Adulto JovenRESUMEN
BACKGROUND: Multiple studies have indicated that genetic components contribute significantly to the risk of rotator cuff tears. Previous studies have suggested that the SAP30BP gene may play an essential role in the development of rotator cuff tears. The aim of this study was to evaluate the potential association of the SAP30BP gene with the susceptibility to rotator cuff tears in a Han Chinese population. METHODS: A total of 394 patients with rotator cuff tears and 998 healthy controls were included in the study. Twelve tag single nucleotide polymorphisms (SNPs) located in the region of the SAP30BP gene were selected for genotyping. Genetic association analyses were performed using χ2 tests for each SNP. Significant associations were searched in the GTEx database for their functional consequences. RESULTS: SNP rs820218 was significantly associated with rotator cuff tears (χ2 = 9.49, P = 0.0021, OR [95% CI] = 0.67 [0.52-0.87]). In addition, SNP rs820218 was found to be significantly associated with the gene expression level of SAP30BP in whole blood (NES = 0.12, P = 1.00 × 10-6). CONCLUSION: Our study has shown that the genetic polymorphism of SAP30BP contributes to the risk of rotator cuff tears in Chinese Han people. Individuals with the A allele for SNP rs820218 were less susceptible to developing rotator cuff tears.
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Estudios de Asociación Genética , Predisposición Genética a la Enfermedad/genética , Proteínas Nucleares/genética , Lesiones del Manguito de los Rotadores/genética , Factores de Transcripción/genética , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , Femenino , Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Proteínas Nucleares/sangre , Polimorfismo de Nucleótido Simple , Factores de Transcripción/sangreRESUMEN
Background: Multiple lines of evidence have suggested that genetic factors may contribute to steroid-induced osteonecrosis of the femoral head (SONFH). Complement receptor 2 (CR2), constituting a family of regulators of complement activation, has been recently reported to be associated with osteonecrosis of the femoral head (ONFH) in Koreans. The aim of this study was to evaluate the relationships between polymorphisms of the CR2 gene and susceptibility to SONFH in the male Han Chinese population. Materials and Methods: A total of 468 SONFH patients and 1224 healthy controls were recruited for this study. Ten tag single nucleotide polymorphisms (SNPs) located within the CR2 gene were genotyped. Genetic association analyses, including SNP and haplotypic analyses, were performed for the 10 SNPs. Furthermore, bioinformatic analyses were conducted to examine the functional consequences of SNPs shown to be significantly associated with SONFH. Results: An intronic SNP, rs311306, was identified to be significantly associated with the risk of SONFH (p = 0.0008, odds ratio = 1.44). Allelic analyses showed that the C allele of this SNP significantly elevated the risk of SONFH, which was replicated in genotypic association analyses. Moreover, a 3-SNP haplotype was significantly associated with SONFH (rs311306-rs17044576-rs3767933, p = 7.49 × 10-8). Furthermore, bioinformatic analyses indicated limited functional consequences of SNP rs311306, but a complex interaction network was constructed for the protein encoded by the SLC44A2 gene and proteins encoded by the CD19, CD81, and C3 genes. Conclusion: Our findings shed new light on the link between the CR2 gene and SONFH in Han Chinese males, providing clues as to the nature of the mechanisms involved in the etiology of ONFH.
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Necrosis de la Cabeza Femoral/genética , Receptores de Complemento 3d/genética , Adulto , Alelos , Pueblo Asiatico/genética , Estudios de Casos y Controles , China/epidemiología , Etnicidad/genética , Cabeza Femoral/metabolismo , Frecuencia de los Genes/genética , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Humanos , Masculino , Persona de Mediana Edad , Oportunidad Relativa , Osteonecrosis/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Complemento 3d/metabolismo , Esteroides/efectos adversos , Esteroides/farmacologíaRESUMEN
OBJECTIVE: To investigate the clinical results of locking compression plate combined with autologous iliac bone graft in the treatment of aseptic ulnar nonunion. METHODS: From March 2009 to July 2017, 22 patients with aseptic ulnar diaphyseal nonunion with complete follow-up data were treated with surgery, including 12 males and 10 females, aged from 16 to 58 (39.7±9.9) years old and ranging in course of disease from 10 to 192 (39.4±55.7) months. There were 15 atrophic nonunions, 5 hypertrophic nonunions and 2 synovial pseudo-articular nonunions. After debridement of the nonunion, locking compression plate was used to fix the nonunion and autogenous iliac bone graft was given. Bone healing rate, surgical complications and clinical results were evaluated. RESULTS: All the patients were followed up, and the duration ranged from 13 to 42 months, with a mean of (22.5±8.2) months, and 1 patient did not heal. Visual analogue pain scores ranged from 0 to 3 (0.9±0.9). Pronation of forearm was 47 to 86 (69.0±14.7) degrees, supination was 35 to 85 (63.0±9.4) degrees, wrist flexion was 20 to 80 (51.0±10.2) degrees, wrist flexion was 32 to 88 (71.0±11.7) degrees, elbow flexion contracture was 0 to 25 (9.0±5.6) degrees, further flexion was 105 to 150 (134.0±13.9) degrees, and grip strength was 87% on the opposite side. According to the Anderson scoring system, 8 cases were excellent, 11 were satisfied, 2 were not satisfied, and 1 was failed. CONCLUSIONS: LCP combined with autologous iliac bone graft can effectively treat aseptic ulna diaphyseal nonunion.
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Fracturas no Consolidadas , Adolescente , Adulto , Placas Óseas , Trasplante Óseo , Diáfisis , Femenino , Fijación Interna de Fracturas , Fracturas no Consolidadas/cirugía , Humanos , Ilion , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Cúbito , Adulto JovenRESUMEN
BACKGROUND: Total hip arthroplasty (THA) relieves pain and restores function in patients with severe rheumatoid arthritis and osteoarthritis. Over the past few decades, several authors have attempted to assess the efficacy and safety of simultaneous bilateral THA compared with staged bilateral THA. The purpose of this meta-analysis is to compare the mortalities and complications between simultaneous bilateral THA and staged bilateral THA. METHODS: A literature search to identify eligible studies was undertaken to identify all relevant articles published until August 2018. We included studies that compared simultaneous bilateral THA and staged bilateral THA and their effects on mortality and complications. The outcomes included mortality, the occurrence of deep venous thrombosis (DVT), the occurrence of pulmonary embolism (PE), respiratory complications, cardiovascular complications, digestive system complications and the occurrence of dislocation. Stata 12.0 was used for the meta-analysis. RESULTS: Nineteen studies involving 59,257 patients were identified; among them, 16,758 patients were selected for treatment with simultaneous bilateral THA, and 42,499 patients were chosen for the purpose of staged bilateral THA. The meta-analysis results demonstrated that there was no significant difference between simultaneous bilateral THA and staged bilateral THA in terms of mortality (risk ratio [RR]â=â1.15, 95% CIâ=â0.76, 1.74; Pâ=â.520). Compared with staged bilateral THA, simultaneous bilateral THA was associated with a reduction in the occurrence of DVT, PE and respiratory complications (Pâ<â.05). There were no significant differences in the cardiovascular complications, digestive system complications or the occurrence of dislocation and infection (Pâ=â.057). CONCLUSIONS: We observed that the prevalence of DVT, PE and respiratory complications was considerably lower with the use of simultaneous bilateral THA than with the use of staged bilateral THA. Thus, simultaneous bilateral THA is a considerably safer procedure than staged bilateral THA in selected THA patients.
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Artritis Reumatoide/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/métodos , Osteoartritis de la Cadera/cirugía , Complicaciones Posoperatorias/epidemiología , Artroplastia de Reemplazo de Cadera/mortalidad , Enfermedades del Sistema Digestivo/epidemiología , Cardiopatías/epidemiología , Humanos , Luxaciones Articulares/epidemiología , Prevalencia , Embolia Pulmonar/epidemiología , Trastornos Respiratorios/epidemiología , Trombosis de la Vena/epidemiologíaRESUMEN
Osteoarthritis (OA) is characterized by articular cartilage degradation and joint inflammation. The purpose of the present study is to elucidate the role of the specific function of PRMT1 in chondrocytes and its association with the pathophysiology of OA. We observed that the expression of PRMT1 was apparently upregulated in OA cartilage, as well as in chondrocytes stimulated with IL-1ß. Additionally, knockdown of PRMT1 suppressed interleukin 1 beta (IL-1ß)-induced extracellular matrix (ECM) metabolic imbalance by regulating the expression of MMP-13, ADAMTS-5, COL2A1, and ACAN. Furthermore, silencing of PRMT1 dramatically declined the production of prostaglandin E2 (PGE2) and nitric oxide as well as the level of pro-inflammatory cytokine IL-6 and TNF-α. Mechanistic analyses further revealed that IL-1ß-induced activation of the Hedgehog/Gli-1 signaling is suppressed upon PRMT1 knockdown. However, the effects of inhibition of PRMT1-mediated IL-1ß-induced cartilage matrix degradation and inflammatory response in OA chondrocytes were obviously abolished by Hedgehog agonist Purmorphamine (Pur). Our data collectively suggest that silencing of PRMT1 exerts anti-catabolic and anti-inflammatory effects on IL-1ß-induced chondrocytes via suppressing the Gli-1 mediated Hedgehog signaling pathway, indicating that PRMT1 plays a critical role in OA development and serves as a promising therapeutic target for OA.
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Cartílago/metabolismo , Condrocitos/metabolismo , Técnicas de Silenciamiento del Gen , Proteínas Hedgehog/metabolismo , Interleucina-1beta/metabolismo , Proteína-Arginina N-Metiltransferasas/genética , Proteínas Represoras/genética , Transducción de Señal , Proteína con Dedos de Zinc GLI1/metabolismo , Cartílago/patología , Condrocitos/patología , Proteínas Hedgehog/genética , Humanos , Inflamación/genética , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/genética , Proteína-Arginina N-Metiltransferasas/metabolismo , Proteínas Represoras/metabolismo , Proteína con Dedos de Zinc GLI1/genéticaRESUMEN
AIM OF THE STUDY: Tumour endothelial cells have been proven to have molecular markers distinct from normal endothelial cells. These specific molecular markers allow for targeting of the tumour vasculature with specific pharmacological vehicles to direct diagnostic or therapeutic modalities at the endothelial cells. By performing a phage display-based screening, this study aimed to identify a certain short peptide that could specifically bind to osteosarcoma vasculature. MATERIAL AND METHODS: We performed in vivo screening in the murine models of osteosarcoma with annular Ph.D.-C7C library in the present study. To explore the in vivo binding specificity of the retrieved peptide, we conjugated the peptide with fluorescein isothiocyanate (FITC) and injected it intravenously into osteosarcoma-bearing BALB-c mice. RESULTS: CTKPDKGYC was the dominant sequence isolated from in vivo screening and was named as NF-1. Fluorescence staining found that FITC-NF-1 peptide could be specifically homed to osteosarcoma vasculature while being almost undetectable in the heart, brain, lung and liver. Simultaneously, a small amount of fluorescence could also be detected in the renal glomerulus and renal tubule but not in renal vascular endothelium, indicating that FITC-NF-1 peptide might be excreted mainly through the renal-urinary route. CONCLUSIONS: Our data suggest that, with high binding specificity to osteosarcoma vasculature, peptide NF-1 may have potential value in early diagnosis or targeted therapy for osteosarcoma.
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Alternations in cartilage chondrocyte phenotype characteristic by the decreased type II collagen and aggrecan together with increased type X collagen synthesis serve as a beacon for osteoarthritis progression. However, little is known about the underlying molecular mechanisms. The current study seeks to discover molecules that involved in osteoarthritic chondrocytes phenotype regulation. Differential proteomics was generated with two-dimensional gel electrophoresis between normal articular cartilage (NAC) and advanced osteoarthritic cartilage (AOC). Those differentially expressed proteins were identified by mass spectrometry. The down-regulation of a neuronal silencer, the REST corepressor (CoREST) in AOC, was verified by Western blot. CoREST silencing was performed in primarily cultured NAC chondrocytes with specific siRNA to reveal the possible involvement of CoREST repression in chondrocyte phenotypic genes modulation. Ninteen differentially expressed proteins were screened and identified. Among these proteins, CoREST, HHL, and zinc finger protein 155 were estimated to be possible gene modulators. CoREST protein level was verified to be down-regulated by 69.5% (p < 0.001) in AOC. In response to CoREST knock-down by 64.8% (p < 0.001) in NAC chondrocytes, the gene expression level of the chondrocyte terminal differentiation marker gene, collagen X was found to be up-regulated by 40.0% (p = 0.017), whereas the chondrocyte differentiation phenotypic genes, collagen II and aggrecan were down-regulated by 71.4% (p < 0.001) and 57.6% (p < 0.001), respectively. The results indicate that the silencing of CoREST by siRNA transfection in NAC may reflect CoREST repression in AOC, which results in phenotypic genes modulation and suggests a homeostatic role of this transcription factor in articular chondrocyte.