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BACKGROUND: Osteosarcoma is the most common primary bone malignancy of adolescents and young adults. METHODS: We analyzed liver X receptor α (LXRα) mRNA expression in 16 pairs of human osteosarcoma tissues and adjacent noncancerous tissues. Moreover, we investigated LXRα's potential role in regulating cell proliferation in Saos-2 and U2OS cells. RESULTS: We found that activation of LXRα, a member of nuclear receptor, was able to inhibit cell proliferation in Saos-2 and U2OS cells. At the molecular level, our results further revealed that expression of tumor suppressor gene, FoxO1, was up-regulated by LXRα activation. LXRα activates FoxO1 transcription through a direct binding on its promoter region. CONCLUSION: LXRα acts as a tumor suppressor for osteosarcoma, which may offer a new way in molecular targeting cancer treatment.
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Fatores de Transcrição Forkhead/metabolismo , Receptores Nucleares Órfãos/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Proliferação de Células , Inibidor de Quinase Dependente de Ciclina p21/genética , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/genética , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/genética , Humanos , Receptores X do Fígado , Receptores Nucleares Órfãos/genética , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Regiões Promotoras Genéticas , Interferência de RNA , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Transcrição Gênica , Regulação para CimaRESUMO
OBJECTIVE: To explore and verify that transient receptor potential vanilloid 4(TRPV4) affects chondrocyte degeneration. METHODS: Neonatal SD rats were selected, primary chondrocytes were extracted, and identified by toluidine blue staining and alcian blue staining;an in vitro chondrocyte inflammation model was constructed by IL-1ß, and TRPV4 inhibitor was used to treat chondrocytes under inflammatory conditions, and the chondrocytes were treated by RT-PCR method was used to detect matrix metallopeptidase 13(MMP-13), a disintegrin and metalloproteinase with thrombospondin 5, (ADAMTS-5)ãnitric oxide synthase 2(NOS2)ãCollagen, type II alpha 1(Col2α1)and aggrecan (Acan) mRNA in chondrocytes; primary chondrocytes were treated with different concentrations of TRPV4 overexpression plasmid, and the optimal overexpression dose was screened. The mRNA expressions of TRPV4, MMP-13, ADAMTS-5, NOS2, Col2α1 and Acan in chondrocytes under the optimal TRPV4 overexpression dose were detected. RESULTS: Toluidine blue staining and Alcian blue staining identified the extracted cells as primary chondrocytes;RT-PCR showed that TRPV4, MMP-13, ADAMTS-5, NOS2 mRNA in chondrocytes treated with TRPV4 inhibitor under inflammatory conditions. The expression of Col2α1 mRNA was significantly decreased (P<0.05), and the expression of Col2α1 mRNA was increased (P<0.05). Although there was no significant difference in the expression of Acan mRNA, the overall trend was also increasing. The expression of Col2α1 and Acan mRNA in chondrocytes was significantly decreased (P<0.05), and the expression of NOS2 mRNA was increased(P<0.05), but there was no significant difference in MMP-13 and ADAMTS-5 (P>0.05). CONCLUSION: Inhibiting the expression of TRPV4 can down-regulate the expression of genes related to chondrocyte degeneration.
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Cartilagem Articular , Condrócitos , Canais de Cátion TRPV , Animais , Ratos , Agrecanas/genética , Agrecanas/metabolismo , Células Cultivadas , Interleucina-1beta/metabolismo , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Ratos Sprague-Dawley , RNA Mensageiro/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
This study systematically reviewed the clinical efficacy of acupuncture for lumbar myofascial pain syndrome. The randomized controlled trials (RCTs) regarding acupuncture for lumbar myofascial pain syndrome were searched in PubMed, Cochrane Library, Web of Science, EMbase, Scopus, China national knowledge infrastructure (CNKI), Wanfang database, VIP database, and China biomedical literature service system (SinoMed) from database inception until August 1st, 2022. The Cochrane's risk of bias assessment tool was used to assess the risk of bias in all included studies, and Review Manager 5.3 software was used for statistical analysis of the extracted data. As a result, 12 RCTs, involving 1 087 patients with lumbar myofascial pain syndrome, were ultimately included. The Meta-analysis results showed that the visual analog scale (VAS) score of pain in the observation group was lower than those in the oral non-steroidal anti-inflammatory medication control [SMD=-1.67, 95%CI (-2.44, -0.90), Z=4.26, P<0.000 1] and other treatment control [low-frequency electrical stimulation, tuina, electromagnetic wave irradiation combined with piroxicam gel, SMD=-1.98, 95%CI (-2.48, -1.48), Z=7.74, P<0.000 01]. The pain rating index (PRI) score in the observation group was lower than those in the lidocaine injection control [MD=-2.17, 95%CI (-3.41, -0.93), Z=3.44, P=0.000 6] and other treatment control [low-frequency electrical stimulation, tuina, MD=-5.75, 95%CI (-9.97, -1.53), Z=2.67, P=0.008]. The present pain intensity (PPI) score in the observation group was lower than that in other treatment control [low-frequency electrical stimulation, tuina, MD=-1.04, 95%CI (-1.55, -0.53), Z=4.01, P<0.000 1]. In conclusion, compared with oral non-steroidal anti-inflammatory medication, low-frequency electrical stimulation, tuina, and electromagnetic wave irradiation combined with piroxicam gel, acupuncture is more effective in reducing pain in patients with lumbar myofascial pain syndrome; acupuncture also exhibites advantage over lidocaine injection in improving PRI score and showed better outcomes over tuina and low-frequency electrical stimulation in improving PRI and PPI scores.
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Terapia por Acupuntura , Síndromes da Dor Miofascial , Humanos , Piroxicam , Terapia por Acupuntura/métodos , Dor , Síndromes da Dor Miofascial/terapia , Anti-Inflamatórios não Esteroides/uso terapêutico , LidocaínaRESUMO
OBJECTIVE: To explore influence of external factors of wind, cold and dampness on clinical symptoms in knee osteoarthritis (KOA) patients with different constitutions of traditional Chinese medicine. METHODS: A cross-sectional stratified study was performed to select 108 patients with Gradeâ ¡KOA in Kellgren & Lawrence (K-L) classification, including 22 males and 86 females, aged from 47 to 75 years old with an average of (60.7±6.0) years old;body mass index(BMI) ranged from 17.87 to 31.22 kg·m-2 with an average of (23.80±2.86) kg·m-2. According to Classification and Judgment of TCM Physique (ZYYXH/T157-2009), the types of TCM physique were determined and divided into 4 layers according to the deficiency and actual physique. Among them, there were 24 patients without biased physique, 12 males and 12 females, aged from 51 to 73 years old with an average of(62.8±6.0) years old, BMI ranged from 17.87 to 31.14 kg·m-2 with an average of (24.32±3.25) kg·m-2;there were 46 patients with virtual bias constitution, including 7 males and 39 females, aged from 47 to 70 years old with an average of (60.0±5.8) years old, BMI ranged from 19.38 to 31.22 kg·m-2 with an average of(23.42±2.97) kg·m-2;There were 26 patients with solid bias constitution, including 2 males and 24 females, aged from 48 to 75 years old with an average of (60.4±5.8) years old, BMI ranged from 21.16 to 30.76 kg·m-2 with an average of (24.15±2.33) kg·m-2;there were 9 patients with special constitution, 1 male and 8 female, aged from 53 to 75 years old with an average of (59.8±7.5) years old, BMI ranged from 19.26 to 26.67 kg·m-2 with an average of (23.79±2.49) kg·m-2. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to evaluate severity of clinical symptoms. The wind-cold-dampness external factor score was calculated through the questionnaire of wind-cold-dampness syndrome scale to evaluate degree of influence of wind-cold-dampness external factor. Pearson correlation analysis and partial correlation analysis were used to calculate the correlation coefficient between severity of external factors affecting wind, cold and dampness and severity of clinical symptoms in patients with different TCM constitution stratification. RESULTS: There was no statistical significance between total score of wind-cold-dampness and WOMAC score in patients with no biased constitution and special condition. Total wind-cold-dampness score of patients with virtual biased constitution was positively correlated with WOMAC stiffness score (r=0.327, P=0.032), and total wind-cold-dampness score of patients with solid biased constitution was positively correlated with WOMAC pain score (r=0.561, P=0.005) and WOMAC overall score (r=0.446, P=0.033). After further adjusting for the interaction of external factors of wind-cold-dampness, there was no statistical significance between wind-cold-dampness scores and WOMAC scores in patients with solid biased constitution. The score of dampness and pathogenic factors was positively correlated with WOMAC stiffness score (r=0.414, P=0.007). CONCLUSION: The external factors of wind-cold dampness have different effects on the clinical symptoms of KOA patients with different TCM constitutions. Compared with other constitutions, the rigid symptoms of patients with asthenic biased constitutions are more susceptible to dampness pathogenic factors.
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Medicina Tradicional Chinesa , Osteoartrite do Joelho , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Síndrome , Vento , Temperatura BaixaRESUMO
OBJECTIVE: To investigate the effects of osthole on chondrocyte proliferation in vitro. METHODS: Primary rat chondrocytes were isolated from the femoral head of newborn rats using collagenase digestion and cultured in Dulbecco's modified Eagle's medium. The proliferation of primary chondrocytes was assessed in second-passage cultures using cell counting kit-8 and the growth curve was drawn. Type II procollagen gene (Col2a1) expression in chondrocytes was also identified using cell immunofluorescence assay. The second-passage chondrocytes were divided into five groups, including control group and osthole groups at 6.25, 12.5, 25 and 50 µmol/L. The growth property of rat chondrocytes was observed after 24, 48 and 72 h of culture with osthole at corresponding dose. Both protein and mRNA expression of proliferating cell nuclear antigen (PCNA) and cyclin D1 was measured by Western blot and polymerase chain reaction methods. RESULTS: The second-passage chondrocytes were viable and showed Col2a1 expression in the cytoplasm. The proliferation of rat chondrocytes was inhibited by osthole in a dose-dependent manner. Meanwhile, there were significant decreases in both protein and mRNA expression of PCNA and cyclin D1 in the osthole groups compared with the control group. CONCLUSION: Osthole exhibits inhibitory effect on proliferation of rat chondrocytes by down-regulating PCNA and cyclin D1 expression.
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Proliferação de Células/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Cumarínicos/farmacologia , Animais , Células Cultivadas , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Ciclina D1/metabolismo , Regulação para Baixo , Antígeno Nuclear de Célula em Proliferação/metabolismo , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Osteoarthritis (OA) is the most prevalent degenerative joint disease. In vitro experiments are an intuitive method used to investigate its early pathogenesis. Chondrocyte inflammation models in rats and mice are often used as in vitro models of OA. However, similarities and differences between them in the early stages of inflammation have not been reported. OBJECTIVE: This paper seeks to compare the chondrocyte phenotype of rats and mice in the early inflammatory state and identify chondrocytes suitable for the study of early OA. METHODS: Under similar conditions, chondrocytes from rats and mice were stimulated using the same IL-1ß concentration for a short period of time. The phenotypic changes of chondrocytes were observed under a microscope. The treated chondrocytes were subjected to RNA-seq to identify similarities and differences in gene expression. Chondrocytes were labelled with EdU for proliferation analysis. Cell proliferation-associated proteins, including minichromosome maintenance 2 (MCM2), minichromosome maintenance 5 (MCM5), Lamin B1, proliferating cell nuclear antigen (PCNA), and Cyclin D1, were analysed by immunocytochemical staining, cell immunofluorescence, and Western blots to verify the RNA-seq results. RESULTS: RNA-seq revealed that the expression patterns of cytokines, chemokines, matrix metalloproteinases, and collagen were similar between the rat and mouse chondrocyte inflammation models. Nonetheless, the expression of proliferation-related genes showed the opposite pattern. The RNA-seq results were further verified by subsequent experiments. The expression levels of MCM2, MCM5, Lamin B1, PCNA, and Cyclin D1 were significantly upregulated in rat chondrocytes (P < 0.05) and mouse chondrocytes (P < 0.05). CONCLUSIONS: Based on the findings, the rat chondrocyte inflammation model may help in the study of the early pathological mechanism of OA.
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Proliferação de Células/genética , Condrócitos/metabolismo , Inflamação , Interleucina-1beta/metabolismo , Osteoartrite/metabolismo , Animais , Ciclina D1 , Modelos Animais de Doenças , Expressão Gênica , Immunoblotting , Imuno-Histoquímica , Interleucina-1beta/genética , Camundongos , Osteoartrite/genética , Antígeno Nuclear de Célula em Proliferação , RNA-Seq , RatosRESUMO
Osteoarthritis (OA) is a degenerative joint disease and is the main cause of chronic pain and functional disability in adults. Articular cartilage is a hydrated soft tissue that is composed of normally quiescent chondrocytes at a low density, a dense network of collagen fibrils with a pore size of 60-200 nm, and aggrecan proteoglycans with high-density negative charge. Although certain drugs, nucleic acids, and proteins have the potential to slow the progression of OA and restore the joints, these treatments have not been clinically applied owing to the lack of an effective delivery system capable of breaking through the cartilage barrier. Recently, the development of nanotechnology for delivery systems renders new ideas and treatment methods viable in overcoming the limited penetration. In this review, we focus on current research on such applications of nanotechnology, including exosomes, protein-based cationic nanocarriers, cationic liposomes/solid lipid nanoparticles, amino acid-based nanocarriers, polyamide derivatives-based nanocarriers, manganese dioxide, and carbon nanotubes. Exosomes are the smallest known nanoscale extracellular vesicles, and they can quickly deliver nucleic acids or proteins to the required depth. Through electrostatic interactions, nanocarriers with appropriate balance in cationic property and particle size have a strong ability to penetrate cartilage. Although substantial preclinical evidence has been obtained, further optimization is necessary for clinical transformation. STATEMENT OF SIGNIFICANCE: The dense cartilage matrix with high-negative charge was associated with reduced therapeutic effect in osteoarthritis patients with deep pathological changes. However, a systematic review in nanodevices for deep cartilage penetration is still lacking. Current approaches to assure penetration of nanosystems into the depth of cartilage were reviewed, including nanoscale extracellular vesicles from different cell lines and nanocarriers with appropriate balance in cationic property and size particle. Moreover, nanodevices entering clinical trials and further optimization were also discussed, providing important guiding significance to future research.
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Cartilagem Articular , Nanotubos de Carbono , Ácidos Nucleicos , Osteoartrite , Adulto , Humanos , Osteoartrite/patologia , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Cátions , Proteínas/farmacologiaRESUMO
The present study was designed to explore the relationship between thrombin and catabolic activity in chondrocytes. Primary rat chondrocytes were cultured for 24 h with rat serum (RS), rat plasma (RP), or rat plasma supplemented with thrombin (RPT). RNA-sequencing was then performed. Cell proliferation was analyzed by EdU uptake, CCK-8 assays and protein-protein interaction (PPI) network of proliferation-related genes. Heatmaps were used to visualize differences in gene expression. Gene Ontology (GO) enrichment analyses of up- and down-regulated differentially expressed genes were conducted. Molecular probes were used to label the endoplasmic reticulum in chondrocytes from three treatment groups. Immunofluorescence and Safranin O staining were used to assess type II collagen (Col2a1) expression and proteoglycan synthesis, whereas Lox expression was assessed by immunocytochemistry. The expression of enzymes involved in the synthesis and maturation of extracellular matrix (ECM) components and chemokines were measured by qPCR while matrix metalloproteinases (MMPs) levels were evaluated by Western blotting. Relevant nodules were selected through further PPI network analyses. A total of 727 and 1162 genes were up- and down-regulated based on the Venn diagrams comparison among groups. Thrombin was thus able to promote chondrocyte proliferation and a shift towards fibrotic morphology, while upregulating MMPs and chemokines linked to ECM degradation. In addition, thrombin decreased the enzyme expression involved in the synthesis and maturation of ECM.
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Condrócitos/citologia , Retículo Endoplasmático/metabolismo , Perfilação da Expressão Gênica/métodos , Trombina/farmacologia , Animais , Proliferação de Células , Células Cultivadas , Quimiocinas/genética , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Meios de Cultura/química , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Metaloproteinases da Matriz/genética , Plasma/química , Cultura Primária de Células , Mapas de Interação de Proteínas , Ratos , Análise de Sequência de RNA , Soro/químicaRESUMO
OBJECTIVE: To study the effects of three different laser treatments (650 nm alone, 10.6 µm alone and combined laser of 650 nm and 10.6 µm) on experimental osteoarthritis of the knees in C57 black mice. METHODS: Sixty C57 black mice were divided randomly into 6 groups. Ten mice were assigned to a normal control group (no intervention) and the other 5 groups were subjected to a forced running regimen to induce osteoarthritis. One group was set as the model control group. The other 4 groups were given 90 s of a 650 nm laser, 90 s of a 10.6 µm laser, 90 s of a combined laser, or a sham treatment on acupoint Dubi (ST35) of the rear left leg 3 times per week for 4 weeks. The modified Mankin score was used to evaluate the degree of cartilage degradation. Immunohistochemical staining for heat shock protein (HSP) 70 was conducted. RESULTS: Mankin scores of the model control group and the sham control group were significantly higher than that of the normal control group (P<0.01). Mankin score of the combined laser group was significantly lower than that of the model control group (P<0.01). Compared with the normal control group, there was a significant induction of HSP70 in the arthritic chondrocytes of the combined laser group. CONCLUSION: The arthritic cartilage induced in C57 black mice improved significantly after combined laser treatment of 650 nm and 10.6 µm lasers. This effect may be related to the induction of HSP70 in the arthritic chondrocytes. The two different lasers appear to have a synergistic effect.
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Terapia por Acupuntura/métodos , Proteínas de Choque Térmico HSP70/metabolismo , Terapia a Laser , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Animais , Cartilagem Articular/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Osteoartrite do Joelho/patologiaRESUMO
OBJECTIVE: To study role of TLR4/NF-κB pathway for early change of synovial membrane in knee osteoarthritis rats. METHODS: Eighteen male SD rats weighted (200±20) g were randomly divided into 2 groups, namely control and model group, and 9 in each group. Knee OA model group was established by using modified Hulth method in model group. Control group was not treated. Synovial tissue and serum was extracted at 4 and 21 d after operation. Expression of CD14, TLR4, IL-1ß, TNF-α, ADAMTS-4, MMP-13 were detected by real-time PCR respectively. NF-κB p65 protein was detected by Western-blot; serum concentrations of haluronic acid (HA), N-propeptide of type III procollagen(PIIINP) was detected by Elisa. RESULTS: Expression of CD14, ADAMTS-4, and NF-κB p65 in model group were higher than that of control group at 4 and 21 days after operation, while expression of TLR4, IL-1ß, TNF-α and MMP-13 were higher than that of control group at 21 days after operation(P<0.01). Concentration of PIIINP and HA in model group were higher than that of control group at 4 days after operation, while there was no significant difference at 21 days after operation. CONCLUSIONS: NF-κB pathway could mediate occurrence of KOA by early activating and triggeringg synovial increasingly secreting inflammatory secretion CD14, TLR4, IL-1ß, TNF-α, ADAMTS-4, MMP-13, PIIINP and HA.
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Osteoartrite do Joelho , Animais , Masculino , NF-kappa B , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial , Receptor 4 Toll-LikeRESUMO
OBJECTIVE: Although chondroprotective activities have been documented for polysaccharides, the potential target of different polysaccharide may differ. The study was aimed to explore the effect of glucan HBP-A in chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs in vivo, especially on the expression of type II collagen. METHODS: Chondrocytes isolated from rabbit articular cartilage were cultured and verified by immunocytochemical staining of type II collagen. Chondrocyte viability was assessed after being treated with HBP-A in different concentrations. Morphological status of chondrocytes-alginate hydrogel constructs in vitro was observed by scanning electron microscope (SEM). The constructs were treated with HBP-A and then injected to nude mice subcutaneously. Six weeks after transplantation, the specimens were observed through transmission electron microscopy (TEM). The mRNA expressions of disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTs-5), aggrecan and type II collagen in both monolayer culture and constructs were determined by real time polymerase chain reaction (PCR). The expression of type II collagen and matrix metalloproteinases-3 (MMP-3) in chondrocyte monolayer culture was also tested through Western blot and enzyme linked immunosorbent assay (ELISA), respectively. RESULTS: MMP-3 secretion and ADAMTs-5 mRNA expression in vitro were inhibited by HBP-A at 0.3 mg/mL concentration. In morphological study, there were significant appearance of collagen in those constructs treated by HBP-A. Accordingly, in both chondrocyte monolayer culture and chondrocytes-alginate hydrogel constructs, the expression of type II collagen was increased significantly in HBP-A group when compared with control group (P<0.001). CONCLUSIONS: The study documented that the potential pharmacological target of glucan HBP-A in chondrocytes monolayer culture and tissue engineered cartilage in vivo may be concerned with the inhibition of catabolic enzymes MMP-3, ADAMTs-5, and increasing of type II collagen expression.
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Cartilagem Articular/fisiologia , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Glucanos/farmacologia , Engenharia Tecidual/métodos , Proteínas ADAM/genética , Proteínas ADAM/metabolismo , Agrecanas/genética , Agrecanas/metabolismo , Alginatos/farmacologia , Animais , Cartilagem Articular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/ultraestrutura , Colágeno Tipo II/genética , Feminino , Ácido Glucurônico/farmacologia , Ácidos Hexurônicos/farmacologia , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Imuno-Histoquímica , Metaloproteinase 3 da Matriz/metabolismo , Camundongos Nus , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , CoelhosRESUMO
OBJECTIVE: To establish a reliable model for drug screening and therapy by culturing rat femoral head and inducing cartilage degeneration quickly in vitro. METHODS: The femoral heads from the same SD rats of two-month old were divided into control group and experimental group respectively. They were cultured with DMEM medium plus 10% fetal bovine serum or DMEM medium plus 10% fetal bovine serum plus 50 ng/ml IL-1ß for three days. Femoral heads were fixed in 4% paraformaldehyde, decalcified, dehydrated, embedded in paraffin and cut into slices. Specimens were stained with Toluidine blue and Safranine O-Fast Green FCF. The protein expression levels of type II collagen, MMP13, Sox9 and ADAMTS5 were analyzed by immunofluorescence. RESULTS: Both the Toluidine blue and Safranine O staining were pale in the margin of femoral heads which were stimulated with IL-1ß for three days compared to that in control group. The Fast Green FCF staining was positive at the edge of the femoral head in experimental group, which indicated that cartilage became degenerated. The expression levels of both type H collagen and Sox9 were decreased significantly while the expression levels of MMP13 and ADAMTS5 were increased in experimental group. CONCLUSION: The model of cartilage degeneration is established by culturing and inducing the degeneration of the femoral heads quickly in vitro.
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Doenças das Cartilagens/metabolismo , Interleucina-1beta/metabolismo , Animais , Doenças das Cartilagens/genética , Colágeno Tipo II/genética , Colágeno Tipo II/metabolismo , Modelos Animais de Doenças , Cabeça do Fêmur/metabolismo , Humanos , Técnicas In Vitro , Interleucina-1beta/genética , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Ratos , Ratos Sprague-Dawley , Fatores de Transcrição SOX9/genética , Fatores de Transcrição SOX9/metabolismoRESUMO
OBJECTIVE: The aim of this cross-sectional study was to examine the relationship among pain and other symptoms intensity, and health-related quality of life (HRQoL) in Chinese patients with knee osteoarthritis (OA). METHODS: The study was cross-sectional, descriptive, and correlational. A convenience sample of 466 patients with knee OA was recruited in the study. Age, gender, body mass index (BMI), duration of disease, and Kellgren- Lawrence (KL) scores were recorded. HRQoL and symptoms were assessed using the 36-item Short Form Health Survey (SF-36) and the Western Ontario and McMaster (WOMAC) index in participants. RESULTS: The sample was predominantly female (82%) with mean age 56.56 years and mean BMI 24.53 kg/m(2). We found that WOMAC subscale scores significantly negative correlated with the majority of SF-36 subscale scores in knee OA patients (P < 0.05). There were no correlations between BMI, duration of disease, KL score and the vast majority of SF-36 subscale scores in patients (P > 0.05). In addition, there was a significant correlation between age and PCS, gender and MCS in patients (P < 0.05). Regression analysis showed, WOMAC subscale scores significantly negative correlated with the vast majority of SF-36 subscale scores. WOMAC-pain score had the strongest relationship with SF-36 PCS and MCS scores. CONCLUSIONS: In summary, pain severity has a greater impact on HRQoL than patient characteristics, other joint symptoms and radiographic severity in Chinese knee OA patients. Relieving of knee symptoms may help to improve patients' HRQOL. The study provided the evidence that relieving pain should be the first choice of therapy for knee osteoarthritis.
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Rheumatoid arthritis fibroblast-like synoviocytes (RAFLSs) proliferate abnormally and resist apoptosis. Bufalin inhibits cell proliferation and induces apoptosis in human cancer cells. In this study, we explored the effects of bufalin on interleukin-1beta (IL-1ß)-induced proliferation and apoptosis of RAFLSs. The cell proliferation and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay and annexin V/propidium iodide staining, respectively. Bufalin dose-dependently inhibited IL-1ß-induced RAFLS proliferation. Mechanistically, bufalin decreased the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor-kappa B (NF-κB), both of which are involved in IL-1ß-mediated RAFLS proliferation. Moreover, bufalin induced apoptosis and mitochondrial damage of RAFLSs, which was associated with Bcl-2 downregulation, Bax upregulation, mitochondrial cytochrome c release, and enhanced cleavages of caspase-3 and poly-(ADP-ribose) polymerase. Collectively, our results reveal that bufalin suppresses IL-1ß-induced proliferation of RAFLSs through MAPK and NF-κB signaling pathways and induces RAFLS apoptosis via the mitochondria-dependent pathway.
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Apoptose/efeitos dos fármacos , Artrite Reumatoide/metabolismo , Bufanolídeos/farmacologia , Interleucina-1beta/antagonistas & inibidores , Membrana Sinovial/efeitos dos fármacos , Membrana Sinovial/metabolismo , Adulto , Apoptose/fisiologia , Artrite Reumatoide/patologia , Células Cultivadas , Feminino , Humanos , Interleucina-1beta/farmacologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: To investigate regulation function of anodonta glucan HBP-A on chondrocytes through Wnt pathway in vitro. METHODS: Rat chondrocytes were cultured and differentiated induced with IL-1beta (10 ng/ml) in vitro. Chondrocytes were divided into five groups:IL-13 group,IL-1beta + IWP-2 (5 microM,Wnt pathway inhibitor) group, IL-1beta + HBP-A (0.3 mg/ml) group and IL-1beta + IWP-2 + HBP-A group. Wnt-3a, beta-catenin (24 h,48 h,72 h) and MMP-13(72 h) genes expression were detected by Rt-PCR, while beta-catenin, MMP-13, Sox-9 and coll-II (48 h) protein expression were measured by Western-blot. RESULTS: After induction of IL-1beta, gene expression of Wnt-3a, beta-catenin and MMP-13 were increased,so were the protein expression of beta-catenin and MMP-13. In contrast,protein expression of Sox-9 and Coll-II were declined. Following addition of HBP-A, Wnt-3a, beta-catenin and MMP-13 were shown as induction of IL-1beta, but protein expression of Sox-9 and Coll-II were upgraded. Combining HBP-A with IWP-2 led to the lowest level in Wnt-3a, beta-catenin gene and beta-catenin protein expression and highest expression of Sox-9 protein. CONCLUSION: HBP-A could not only delay the differentiation of chondrocytes through downgrading the signal expression of Wnt/beta-catenin,but also adjust the expression of Wnt-3a, beta-catenin and Sox-9 when combinated with the Wnt inhibitor.
Assuntos
Anodonta/química , Condrócitos/metabolismo , Glucanos/farmacologia , Proteína Wnt3A/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Interleucina-1beta/metabolismo , Ratos , Via de Sinalização Wnt/efeitos dos fármacos , Proteína Wnt3A/genética , beta Catenina/metabolismoRESUMO
OBJECTIVE: To observe the distribution features of tender points in knee of patients with knee osteoarthritis in order to provide evidences for the treatment and diagnosis. METHODS: From November 2011 to December 2012,86 patients with knee osteoarthritis were recruited, including 21 males and 65 females, ranging in age from 45 to 85 years old, with an average of (59.98 +/- 8.23) years old. The course of disease ranged from 3 months to 15 years. The tender points and its distributions were determined by finger press carefully on their knees. Data of studying was analyzed by frequency statistics and Hierachical cluster analysis. RESULTS: The distribution of tender points in the knee osteoarthritis was mainly in the interior region and anterior area such as in apex of patella, adductor tubercle and et al. According to the results of hierachical cluster analysis, the tender points could be divided into two categories the first cluster was in the interior region of knee, the second cluster was in the lateral region. CONCLUSION: The findings demonstrated that cluster analysis statistical method can be used for classification of the distribution of tender points. The distribution features of tender points in knee osteoarthritis are related to the anatomic site in knee.
Assuntos
Osteoartrite do Joelho/complicações , Dor/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Effective biomarkers for clinical usage of osteoarthritis are still limited. It was confirmed that C-terminal crosslinking telopeptide of type I collagen (CTX- II) was a specific marker reflecting degradation of articular cartilage. Detection of CTX- II could promptly reflect level of cartilage injury and degradation ,diagnose OA,predict its progress,monitor effects of drug treatment, thus, reflect the condition of osteoarthritis patient indirectly. Application of CTX- II focused mainly on in the early stage of OA and need together to detect with other biomarkers,in order to more accurately reflection of the pathological changes of OA,but the specific clinical significance of CTX- II results still need to improve further.
Assuntos
Biomarcadores/análise , Colágeno Tipo II/análise , Osteoartrite/diagnóstico , Fragmentos de Peptídeos/análise , Cartilagem Articular/patologia , Diagnóstico Precoce , HumanosRESUMO
BACKGROUND: To evaluate the diagnostic utility of conventional ultrasonography and real time ultrasound elastography in differentiating degenerating cystic thyroid nodules mimicking malignancy from papillary thyroid carcinoma. METHODS: We retrospectively analyzed conventional ultrasonographic and elastographic characteristics of 19 degenerating cystic thyroid nodules mimicking malignancy in 19 patients, with 30 surgically confirmed PTCs as controls. Based on size, the nodules had been grouped into less than 10mm (group A) and greater than 10 mm (group B). We evaluated conventional parameters and elasticity pattern. Color-scaled elastograms were graded as to stiffness of nodules using an elasticity pattern from I (soft) to IV (stiff). RESULTS: Degenerating cystic thyroid nodules were similar to PTCs in conventional ultrasonographic findings, but the former frequently showed oval to round in shape (group A, 69.2% vs 18.8%, P=0.017; group B, 66.7% vs 7.14%, P=0.017) and punctuate hyperechoic foci (group A, 61.5% vs 0, P<0.001; group B, 50% vs 0, P<0.001). On real time ultrasound elastography, 7 of 13 degenerating cystic thyroid nodules in group A were pattern I, 5 were pattern II, 1 was pattern III. One degenerating cystic thyroid nodule in group B was pattern II, 5 were pattern III. The area under the curve for elastography was 0.98 in group A (sensitivity 92.3%, specificity 100%, P = 0.002), and 0.88 in group B (sensitivity 16.7%, specificity 100%, P = 0.014). CONCLUSIONS: As a dependable imaging technique, elastography helps increase the performance in differential diagnosis of degenerating cystic thyroid nodule and malignancy.
Assuntos
Carcinoma/diagnóstico por imagem , Carcinoma/diagnóstico , Técnicas de Imagem por Elasticidade , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico , Nódulo da Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico , Adulto , Idoso , Carcinoma/cirurgia , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/diagnóstico por imagem , Carcinoma Papilar/cirurgia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Câncer Papilífero da Tireoide , Glândula Tireoide/diagnóstico por imagem , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To explore the diagnostic value of whole-organ magnetic resonance imaging score (WORMS) in knee osteoarthritis (KOA). METHODS: From November 2009 to January 2011,70 patients with KOA combined with knee effusion among outpatient and inpatient were analyzed retrospectively. Among the patients, 12 patients were male, 58 patients were female,ranging in age from 46 to 75 years,with a mean age of (59.66 +/- 9.93) years. The clinical symptoms were evaluated by WOMAC, the imaging of KOA was assessed by K-L score and WORMS, and COMP and CTX- II were measured respectively by ELISA. The correlation analyses and multiple linear regression analysis were studied to determine associations among biomarkers, clinical variables and radiographic findings of knee joints. RESULTS: The average scores of WOMAC and WORMS were (57.50 +/- 8.20) and (64.54 +/- 16.45) respectively. The median of CTX- II nd COMP were 2.42 ng/ml and 4.56 ng/ml respectively. Grouped by less than the lowest quartile and more than the highest quartile of WORMS, COMP was significantly different (Z=2.04, P=0.039), but there was no significant difference in CTX-II (Z=0.79, P=0.427). WORMS were positively correlated with WOMAC and K-L score (r=0.777, P<0.01; r=0.716, P<0.01; respectively); WOMAC was also positively correlated with K-L score (r=0.692, P<0.01). WORMS's cartilage, osteophytes and synovitis were positively correlated with WOMAC, K-L score and COMP respectively (r=0.771, P<0.01; r=0.509, P<0.01; r=0.917, P<0.01). It was determined by stepwise regression that the KOA was mainly affected by WORMS, K-L score (P=0.015, P=0.025 respectively) when WOMAC as a dependent variable, age, gender, K-L score, WORMS, COMP and CTX- II as independent variables (F=20.327, P<0.01). CONCLUSION: WORMS has a better reference value for diagnosis of KOA. The expression of COMP is high in the synovial fluid when WORMS at the high point. The clinical symptoms of knee osteoarthritis are mainly affected by WORMS and K-L score.