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Osteoarthritis (OA) is a progressive age-related disease characterised by pathological changes in the synovium, articular cartilage, and subchondral bone, significantly reducing the patients' quality of life. This study investigated the role of glucocorticoids, specifically dexamethasone, in OA progression, with a particular focus on their effects on chondrocytes. Although glucocorticoids are commonly used for OA pain relief, our research demonstrated that high concentrations of dexamethasone may accelerate OA progression by enhancing the ability of reactive oxygen species to inhibit chondrocyte autophagy, resulting in cell death and accelerated cartilage degeneration. Despite reports on the acceleration of pathogenesis and cartilage damage in some patients of OA taking corticosteroids, the mechanism behind the same has not been investigated. This necessitates an investigation of the concentration-dependent changes in the cartilage cells upon dexamethasone administration. In addition, the protective effect of PPAR γ on chondrocytes can prevent the decrease in chondrocyte autophagy and delay cartilage degeneration. Therefore, our study suggests that the therapeutic use of glucocorticoids in OA treatment should be more nuanced considering their potential detrimental effects. Future investigations should focus on the mechanisms underlying the glucocorticoid-mediated modulation of cell death processes, which could provide insights into new therapeutic strategies for OA treatment.
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Cartilagem Articular , Osteoartrite , Humanos , Glucocorticoides/farmacologia , Condrócitos , PPAR gama/metabolismo , Piroptose , Qualidade de Vida , Estresse Oxidativo , Osteoartrite/induzido quimicamente , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Autofagia , Dexametasona/farmacologiaRESUMO
PURPOSE: This study aimed to investigate postoperative patient satisfaction at mid- to long-term follow-up after proximal fibular osteotomy and to identify risk factors for patient dissatisfaction. METHODS: This was a retrospective cross-sectional study that included 252 knees from 160 osteoarthritis (OA) patients who underwent proximal fibular osteotomy with a follow-up of four to eight years. Patients were categorized into a satisfied group (satisfaction score ≥ 20) or a dissatisfied group (satisfaction score < 20) based on the New Knee Society Score (New KSS). Patient demographics, preoperative pain visual analogue scale (VAS) score, preoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Kellgren-Lawrence (K-L) grade, preoperative hip-knee-ankle (HKA) angle, and preoperative medial proximal tibial angle (MPTA) were compared between the two groups. Multiple logistic regression analysis was used to identify risk factors for patient dissatisfaction. RESULTS: Of the 203 knees, 130 (64.0%) were satisfied with their results. Multiple logistic regression analysis demonstrated that severe medial OA (K-L grade = IV) was an independent risk factor for patient dissatisfaction after proximal fibular osteotomy (OR 8.334, 95% CI 3.815-18.206, P < 0.001). CONCLUSION: Our study confirmed that proximal fibular osteotomy was a simple and effective treatment for medial OA patients, and majority of our patients obtained a higher satisfaction rate within mid- to long-term follow-up after surgery. Severe medial OA, however, was an independent risk factor for dissatisfaction.
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Osteoartrite do Joelho , Humanos , Osteoartrite do Joelho/cirurgia , Osteoartrite do Joelho/etiologia , Seguimentos , Estudos Retrospectivos , Estudos Transversais , Satisfação do Paciente , Articulação do Joelho/cirurgia , Tíbia/cirurgia , Osteotomia/efeitos adversos , Osteotomia/métodosRESUMO
BACKGROUND/AIM: Osteoarthritis (OA) is a common degenerative disease characterized by cartilage degradation and inflammation. This study aimed to investigate the anti-inflammatory properties of formononetin, an isoflavone extracted from astragalus membranaceus, on OA. METHODS: Human OA chondrocytes were pretreated in vitro with formononetin and subsequently stimulated with IL-1ß. The production of inflammatory mediators, cytokines and the synthesis of catabolic factors were evaluated by ELISA and Western blot analysis. In addition, a rat model of OA was established and treated with formononetin. RESULTS: Formononetin attenuated the overproduction of inflammatory mediators and cytokines, suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase, and inhibited the synthesis of catabolic factors such as MMPs and thrombospondin motifs 5. Furthermore, formononetin exerted protective effects in a rat model of OA. Mechanistically, we found that formononetin inhibited IL-1ß induced activation of nuclear factor kappa B and AKT by activating the phosphatase and tensin homolog. CONCLUSIONS: Formononetin could be used as a potential agent for OA treatment.
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Isoflavonas , Osteoartrite , Humanos , Ratos , Animais , Condrócitos , NF-kappa B/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interleucina-1beta/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Inflamação/metabolismo , Mediadores da Inflamação/metabolismo , Células Cultivadas , PTEN Fosfo-Hidrolase/metabolismoRESUMO
Osteoarthritis (OA) is a frequently observed condition in aged people. OA cartilage is characterized by chondrocyte apoptosis, chondrocyte inflammation, and hyperactive catabolism of extracellular matrix. However, the specific molecular mechanisms remain unclear. Recent data has shown that Angptl4, a multifunctional cytokine, is involved in the regulation of inflammatory and apoptosis responses in different tissues. This study is aimed at defining the role of Angptl4 in the development of OA. We employed X-ray analysis, safranin O-fast green (S-O) staining, and hematoxylin staining to evaluate histomorphological characteristics in the knee joint of mice. Real-time quantitative polymerase chain reaction, Western blot assays, immunofluorescence staining, and enzyme-linked immunosorbent assays (ELISA) were performed to analyze the changes in gene and protein expression. Mechanically, our data demonstrated that Angptl4 knockdown improved the degradation of extracellular matrix and reduced TNF-α-mediated chondrocyte inflammation and apoptosis by suppressing sirtuin 1/NF-κB signaling pathway. In addition, animal studies showed that the suppression of Angptl4 expression might alleviate OA development. In conclusion, our findings revealed the underlying mechanisms of Angptl4 regulation in chondrocytes and its potential value in the treatment of OA.
Assuntos
Proteína 4 Semelhante a Angiopoietina , NF-kappa B , Osteoartrite , Proteína 4 Semelhante a Angiopoietina/genética , Animais , Apoptose , Células Cultivadas , Matriz Extracelular/metabolismo , Inativação Gênica , Humanos , Inflamação/genética , Inflamação/metabolismo , Camundongos , NF-kappa B/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismoRESUMO
Osteoarthritis (OA) is a complex condition that involves both apoptosis and senescence and currently cannot be cured. Fibroblast growth factor 21 (FGF21), known for its role as a potent regulator of glucose and energy metabolism, protects from various diseases, possibly by mediating autophagy. In the present study, the role of FGF21 in the progression of OA was investigated in both in vitro and in vivo experiments. In vitro, the results revealed that FGF21 administration alleviated apoptosis, senescence, and extracellular matrix (ECM) catabolism of the chondrocytes induced by tert-butyl hydroperoxide (TBHP) by mediating autophagy flux. Furthermore, CQ, an autophagy flux inhibitor, could reverse the protective effect of FGF21. It was observed that the FGF21-induced autophagy flux enhancement was mediated by the nuclear translocation of TFEB, which occurs due to the activation of the SIRT1-mTOR signaling pathway. The in vivo experiments demonstrated that FGF21 treatment could reduce OA in the DMM model. Taken together, these findings suggest that FGF21 protects chondrocytes from apoptosis, senescence, and ECM catabolism via autophagy flux upregulation and also reduces OA development in vivo, demonstrating its potential as a therapeutic agent in OA.
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Apoptose , Senescência Celular , Matriz Extracelular/metabolismo , Fatores de Crescimento de Fibroblastos/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologia , Sirtuína 1/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína ADAMTS5/metabolismo , Agrecanas/metabolismo , Animais , Autofagia/efeitos dos fármacos , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Caspase 3/metabolismo , Senescência Celular/efeitos dos fármacos , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Colágeno Tipo II/metabolismo , Feminino , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína X Associada a bcl-2/metabolismo , terc-Butil Hidroperóxido/toxicidadeRESUMO
Osteoarthritis (OA), a common degenerative joint disease, is principally characterized by inflammation and destruction of cartilage. Nobiletin, an extract of the peel of citrus fruits, is known to have anti-inflammatory properties. However, the mechanisms by which nobiletin plays a protective role in osteoarthritis (OA) are not completely understood. In the present study, we investigated the anti-inflammatory effects of nobiletin in the progression of OA in both in vitro and in vivo experiments. Mouse chondrocytes were pretreated with nobiletin (0, 10, 20, 40 µM) for 24 h and then incubated with IL-1ß (10 ng/ml, 24 h) in vitro. The generation of PGE2 and NO was evaluated by the Griess reaction and ELISAs. The protein expression of inducible nitric oxide synthase, matrix metalloproteinase-3, matrix metalloproteinase-13, A disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS5), cyclooxygenase-2, collagen II, and aggrecan was analyzed by Western blotting. Immunofluorescence and Western blot analysis were used to detect nuclear factor-κB (NF-κB) signaling molecules. Induction of proinflammatory and catabolic mediators by IL-1ß stimulation of mouse chondrocytes could be partially blocked by treatment with nobiletin or ammonium pyrrolidine dithiocarbamate (an NF-κB inhibitor). Furthermore, our results indicated that nobiletin exhibited a therapeutic effect through active inhibition of the NF-κB signaling pathway. In a mouse model of OA, injection of nobiletin (20 mg/kg) every 2 days for 8 weeks after surgery inhibited cartilage destruction and synovitis. Taken together, our findings suggest that nobiletin may be a potential therapeutic agent for the treatment of OA.
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BACKGROUND: Breast cancer (BC) displays striking genetic, epigenetic and phenotypic diversity. N6-methyladenosine (m6A) in mRNA has emerged as a crucial epitranscriptomic modification that controls cancer self-renewal and cell fate. However, the key enzymes of m6A expression and function in human breast carcinogenesis remain unclear. METHODS: The expression of m6A methylases (METTL3, METTL14 and WTAP) and demethylases (FTO and ALKBH5) were analyzed by using ONCOMINE and The Cancer Genome Atlas databases and in 36 pairs of BC and adjacent non-cancerous tissue. The level of m6A in BC patients was detected by ELISA, and the function of m6A was analyzed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and transwell assay. The database of bc-GenExMiner v4.0, Kaplan-Meier Plotter and cBioPortal were queried for correlation, mutation and prognosis analysis of BC. RESULTS: The m6A methylases and demethylases were dysregulated in several major malignant tumors. Specifically, the expression of all m6A methylases was reduced in BC as compared with normal controls, but the demethylase ALKBH5 was induced in ONCOMINE databases and confirmed in clinical patients. METTL14 expression was positively correlated with METTL3 expression, and both showed high expression in normal breast-like and luminal-A and -B BC. Functionally, reducing m6A expression by overexpressing METTL14 and/or knockdown of ALKBH5 could inhibit breast cell viability, colony formation and cell migration. Furthermore, Kaplan-Meier, meta-analysis and univariate Cox assay showed that the expression of m6A members including METTL3, METTL14, WTAP and FTO but not their gene mutation and amplification, was tightly associated with cancer progression and poor survival. CONCLUSIONS: Changes of m6A modulators reduced m6A may promote tumorigenesis and predict poor prognosis in BC.
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Adenosina/análogos & derivados , Neoplasias da Mama/patologia , Metiltransferases/metabolismo , Oxirredutases N-Desmetilantes/metabolismo , Adenosina/metabolismo , Adulto , Mama/patologia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Carcinogênese/genética , Linhagem Celular Tumoral , Conjuntos de Dados como Assunto , Progressão da Doença , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Metilação , Metiltransferases/genética , Pessoa de Meia-Idade , Mutação , Oxirredutases N-Desmetilantes/genética , Prognóstico , RNA Mensageiro/metabolismoRESUMO
The anti-inflammatory effect of sinapic acid (SA) has been reported in several studies. However, whether SA has the same effect on osteoarthritis (OA) has yet to be clearly elucidated. We designed a series of in vitro and in vivo procedures to verify the above conjecture. Compared with controls, SA-pretreated human chondrocytes showed lower levels of interleukin (IL)-1ß-induced IL-6, prostaglandin E2 (PGE2), nitric oxide (NO) and tumour necrosis factor-α (TNF-α) in vitro. Meanwhile, SA could also reverse the degradation of type II collage and aggrecan, as well as the overproduction of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-13 (MMP-13), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and a disintegrin and metalloproteinase thrombospondin motifs (ADAMTS)-5. Furthermore, activation of nuclear factor κB (NF-κB), which was induced by IL-1ß, was also inhibited by SA through the pathway of nuclear factor-erythroid 2-related factor-2 (Nrf2)/heme oxygenase 1. In vivo, SA could delay the progress of mice OA models. We propose that SA may be applied as a potential therapeutic drug in OA treatment.
Assuntos
Ácidos Cumáricos/farmacologia , Osteoartrite/tratamento farmacológico , Substâncias Protetoras/farmacologia , Animais , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND: Osteoarthritis (OA) is a type of degenerative joint disease affecting millions of individuals worldwide. However, there are currently no great inflammatory treatments available for it. Sophocarpine (SPC), one of the key bioactive compounds derived from Sophora flavescens, has shown remarkable anti-inflammatory effects. METHODS: In this study, we evaluated the effect of SPC on preventing the progression of OA and investigated its molecular target involved. In brief, rat chondrocytes were pretreated with SPC and subsequently stimulated with IL-1ß. We found that SPC reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). SPC also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SPC promoted the expression of anabolic factors Sox-9 and aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases 13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) in rat chondrocytes. Mechanistically, we found that SPC inhibited nuclear factor kappa B (NF-κB) via the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The beneficial effects of SPC were also observed in vivo using a rat OA model. CONCLUSIONS: Our findings indicate that SPC may be a potential novel therapeutic in the treatment of OA.
Assuntos
Alcaloides/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Condrócitos/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Animais , Células Cultivadas , Condrócitos/fisiologia , Ciclo-Oxigenase 2/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-1beta/imunologia , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Sophora/imunologiaRESUMO
The original version of this article contained mistakes, and the authors would like to correct them. The correct details are given below: ⢠Fig.4 A. In the GPO group, the S-O and H-E staining pictures were used incorrectly. This is our mistake. Now correct the correct pictures.
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BACKGROUND/AIMS: Osteoarthritis is a degenerative joint disease characterized by cartilage degeneration and a chondrocyte inflammatory response that induces an inflammatory environment closely linked to extracellular matrix (ECM) degradation. Ligustilide (LIG) is a major component of the herb Radix Angelicae Sinensis, with demonstrated anti-inflammatory effects. To confirm whether LIG has an equally inhibitory effect on inflammation in human osteoarthritis chondrocytes, we performed in vivo and in vitro experiments to validate the above conjectures and determine the relevant mechanisms. METHODS: Quantitative realtime PCR and western blotting were performed to evaluate the expression of MMP-3, MMP-13, ADAMTS-5, iNOS, and COX-2 at both gene and protein levels. An enzyme-linked immunosorbent assay was used to evaluate the levels of other inflammatory factors (PGE2, TNF-α, and IL-6). The PI3K/AKT and nuclear factor kappa B (NF-κB) signaling pathways were also analyzed by western blotting, whereas immunofluorescence was used to assess the expression of collagen II and aggrecan. The in vitro effect of LIG was evaluated by intraperitoneal injection into a mouse osteoarthritis model induced by destabilization of the medial meniscus. RESULTS: LIG lowered the phosphorylation levels of p65, IκBα, and IKKα/ß and suppressed the IL-1ß-induced expression of MMP-3, ADAMTS-5, iNOS, and COX-2 and the inflammatory factors PGE2, TNF-α, and IL-6. LIG markedly decreased IL-1ß-induced degradation of collagen II and aggrecan. In vivo results showed that LIG-treated mouse cartilage showed less damage than the control group; the Osteoarthritis Research Society International (OARSI) score was also lower. LIG further reduced the thickness of the subchondral bone plate and alleviated the synovitis. CONCLUSION: LIG may act as a promising therapeutic agent for osteoarthritis by attenuating IL-1ß-induced inflammation in chondrocytes and ECM degradation via suppression of NF-κB activation by the PI3K/AKT pathway.
Assuntos
4-Butirolactona/análogos & derivados , Osteoartrite/prevenção & controle , 4-Butirolactona/química , 4-Butirolactona/farmacologia , 4-Butirolactona/uso terapêutico , Proteína ADAMTS5/metabolismo , Idoso , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/citologia , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/análise , Modelos Animais de Doenças , Humanos , Interleucina-1beta/farmacologia , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Inibidor de NF-kappaB alfa/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/metabolismo , Osteoartrite/patologiaRESUMO
BACKGROUND: Osteoarthritis (OA) is a common degenerative joint disease for which currently no anti-inflammatory therapy is available. Sauchinone (SAU), a key bioactive compound derived from Saururus chinensis, which has shown remarkable anti-inflammatory effects. METHODS: To evaluate the effect of SAU on OA progression, mouse chondrocytes were pretreated with SAU and subsequently stimulated with interleukin (IL)-1ß. We found that SAU reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and IL-6. SAU also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SAU promoted the expression of aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases (MMPs) and thrombospondin motifs 5 (ADAMTS-5) in mouse chondrocytes. Col X, vascular endothelial growth factor-A (VEGF)-A, and Runx2, major markers of hypertrophic chondrocytes, were markedly elevated following IL-1ß stimulation, and were reduced by SAU treatment while having the opposite effect on Col II. Mechanistically, we found that SAU inhibited nuclear factor kappa B (NF-κB) and activated the Nrf2/HO-1 pathway. The beneficial effects of SAU were also observed in vivo using a mouse OA model. CONCLUSIONS: Our findings indicate that SAU may be a potential novel therapeutic for the treatment of OA.
Assuntos
Anti-Inflamatórios/uso terapêutico , Benzopiranos/uso terapêutico , Condrócitos/efeitos dos fármacos , Dioxóis/uso terapêutico , Interleucina-1beta/imunologia , Osteoartrite , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/imunologia , Condrócitos/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/imunologia , Matriz Extracelular/metabolismo , Feminino , Heme Oxigenase-1/metabolismo , Interleucina-1beta/farmacologia , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/imunologia , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: We studied anteromedial varus angulation (VA) in the proximal third of the ulna. The importance of restoration of the anatomical orientation of the ulnar after a proximal fracture is unclear. The purpose of this study was to evaluate the impact of minimal proximal ulna malunion on elbow function after a proximal ulna fracture. METHODS: We reviewed the follow-up of 60 patients who had undergone open reduction with internal fixation (ORIF) of a proximal fracture of the ulna. Patients were divided into two groups, defined as either more or less than 5° of the difference between the VA of the fractured and contralateral ulna. The range of motion(ROM)of elbow flexion, extension and forearm rotation on both sides, Mayo Elbow Performance Score (MEPS) and Visual Analogue Scale (VAS) were measured. RESULTS: The average postoperative time was 3.1 years (1-5 years). Mean VA of the fractured arm was different from the normal side (7.8 ± 3.0 vs 12.7 ± 3.0). Compared to the unfractured arm there was a loss in mean elbow flexion (14.2 ± 4.9 vs 18.0 ± 5.9), extension ROM (7.1 ± 2.5 vs 9.3 ± 1.9, p < 0.05) and forearm rotation ROM (15.6 ± 8.6 vs 21.8 ± 9.5) that were statistically significant (p < 0.05). There were no statistically significant differences in the MEPS and VAS score results between the two groups (p > 0.05). CONCLUSIONS: The function of the elbow and forearm was restricted after VA malunion in the proximal ulna, but the quality of life of these patients had not been significantly affected. We suggest that orthopedic surgeons should assess whether the specialized structures of the proximal ulna are damaged or not before surgery. If the anatomy of the fractured bone cannot be restored through manipulation of the connected end directly, it is better to image the anatomical structure of the healthy side from using an elbow X-ray before surgery, and then reset using a pre-shaped plate to prevent malunion.
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Articulação do Cotovelo/fisiopatologia , Fraturas da Ulna/reabilitação , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Fraturas da Ulna/fisiopatologia , Fraturas da Ulna/cirurgiaRESUMO
Osteoarthritis (OA) is an age-related degenerative disease and is the fourth major cause of disability, but there are no effective therapies because of its complex pathology and the side effects of the drugs. Previous research demonstrated that inflammation and ECM degradation play major roles in OA development. Monascin is an azaphilonoid pigment extracted from Monascus-fermented rice with a potential anti-inflammatory effect reported in various preclinical studies. In the present study, we investigated the protectiveness of monascin on interleukin (IL)-1ß-induced mouse chondrocytes and surgical destabilization of the medial meniscus mouse (DMM) OA models. In vitro, monascin treatment inhibited the IL-1ß-induced expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). In addition, the IL-1ß-stimulated matrix metalloproteinase-13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) upregulation and type two collagen and aggrecan degradation were reversed by monascin. Mechanistically, we revealed that monascin suppressed nuclear factor kappa B (NF-κB) signalling by activating the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in IL-1ß-induced chondrocytes. And monascin-induced protectiveness in OA development was also shown by using a DMM model. Altogether, our results suggested that monascin could be a novel therapeutic approach for OA.
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Condrócitos/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Interleucina-1beta/metabolismo , Osteoartrite/tratamento farmacológico , Animais , Condrócitos/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Interleucina-1beta/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , Osteoartrite/genética , Osteoartrite/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
Osteoarthritis (OA) is a chronic degenerative joint disease that is principally characterized by progressive joint dysfunction and cartilage degradation. Inflammation and apoptosis play critical roles in the progression of OA. Geniposide (GPO), one of the principal components of the fruit of Gardenia jasminoides Ellis, has been reported to have anti-inflammatory and other pharmacological effects. In this study, we performed in vitro experiments on rat chondrocytes to examine the therapeutic effects of GPO on OA and investigated its effects in vivo in a rat model of OA induced by medial meniscal tear (MMT). The results suggest that GPO can inhibit the expression of INOS, COX-2, and MMP-13 in vitro, and promote the expression of collagen II in rat chondrocytes stimulated with interleukin-1ß (IL-1ß). In addition, we also found that GPO can inhibit the expression of pro-apoptotic proteins such as Bax, Cyto-c, and C-caspase3 and increase the expression of the anti-apoptotic protein Bcl-2. These changes may be related to GPO-induced inhibition of the IL-1ß-induced activation of the PI3K/Akt/NF-κB signaling pathway. In vivo, we also found that GPO can limit the development of OA in a rat model. Taken together, the above results indicate that GPO has potential therapeutic value for treating OA.
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Apoptose/efeitos dos fármacos , Condrócitos/patologia , Inflamação/tratamento farmacológico , Iridoides/farmacologia , Osteoartrite/tratamento farmacológico , Transdução de Sinais , Animais , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Inflamação/induzido quimicamente , Interleucina-1beta/farmacologia , Iridoides/uso terapêutico , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , RatosRESUMO
BACKGROUND: Fixation of radial neck fractures can be achieved with a plate and screw construct or with two screws. This study evaluated the biomechanical properties of three different fixation methods following radial neck fractures. METHODS: Twenty-four fourth-generation composite radii were sawed to simulate an unstable radial neck fracture. They were then instrumented with a plate and screw construct or two different orientations (crossed and parallel) of screw fixation. Implants were tested under bending and torsional loads via a tension torsion composite test system. Bending and torsional failure loads were added to the remaining implant-radius constructs if they did not fail during the previous tests. RESULTS: During the bending loading test, the crossed-screw group showed the greatest stiffness, followed by the parallel-screw group, the plate group demonstrating the weakest stiffness. There was no significant difference between the crossed- and the parallel-screw groups. However, there was a significant difference between the two screw groups and the plate group. During the bending failure test, the largest stiffness was found for the crossed-screw group, while the plate group exhibited the smallest stiffness. There was a significant difference between the three groups. During the torsion loading test, the highest stiffness was observed for the crossed-screw group, while the plate group showed the lowest stiffness. In the torsion failure test, the failure torques were 11.97 ± 2.659, 8.531 ± 1.768, and 7.079 ± 1.666 N m respectively for the crossed-screw, parallel-screw, and plate groups. There was a significant difference between the crossed-screw group and the two other groups. CONCLUSIONS: Crossed screws and plate fixation are commonly used in clinical practice to treat simple radial neck fractures. While the present study shows that the parallel-screw method results in similar biomechanical strength as the two other techniques, it has the advantages of reaching limited wound exposure and having the implant buried. Therefore, it may be widely used in clinical practice.
Assuntos
Placas Ósseas/normas , Parafusos Ósseos/normas , Fixação Interna de Fraturas/métodos , Teste de Materiais/normas , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Fenômenos Biomecânicos/fisiologia , Fixação Interna de Fraturas/instrumentação , Humanos , Teste de Materiais/métodosRESUMO
BACKGROUND: Screw fixation is a common method used for the treatment of Mason type II radial head fractures. The purpose of our study was to evaluate the mechanical properties of three different screw orientations used for fixation of Mason type II radial head fractures. METHODS: We sawed 24 medium-frequency fourth-generation Synbone radial bones to simulate unstable radial head fractures, which we then fixed with three different screw orientations. Implants were tested under axial load by the tension-torsion composite test system. If the implant-radial constructs did not fail after the axial load test, an axial failure load was added to the remaining constructs. RESULTS: The stiffness of the divergent group was the highest of the three orientations, and this group had statistically significant difference from the other two groups (p < 0.05). However, there was no statistically significant difference between the convergence group and the parallel group (p > 0.05). When the displacement reached 2 mm, the load of the divergent screw was still larger than the other two groups (p < 0.05). CONCLUSIONS: The divergent screw orientation was the most stable and had the greatest control of Mason type II fractures of these three groups. Therefore, it can be better applied in clinical settings.
Assuntos
Parafusos Ósseos , Fixação Interna de Fraturas/métodos , Fraturas do Rádio/cirurgia , Fenômenos Biomecânicos , Fixação Interna de Fraturas/instrumentação , Humanos , Teste de Materiais/métodos , Orientação , Radiografia , Fraturas do Rádio/diagnóstico por imagem , Suporte de CargaRESUMO
Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. α-Mangostin (α-MG), which can be isolated from the fruit of the tropical evergreen tree Garcinia mangostana-L, is known to have anti-inflammatory properties. The aim of the study was to investigate the use of α-MG in the treatment of OA, using both rat chondrocytes and an OA rat model induced by destabilization of the medial meniscus (DMM). Rat chondrocytes were pretreated with α-MG (0, 1.25, 2.5, and 5.0µg/ml for 24h) prior to stimulation with interleukin-1ß (IL-1ß) (10ng/ml for 24h). Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2) was assessed using an enzyme-linked immunosorbent assay (ELISA). The expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase-3, -9, and -13 (MMP-3, MMP-9, and MMP-13), Collagen II, and Aggrecan were detected by both quantitative real-time PCR (qRT-PCR) and a western blot analysis. Nuclear factor-κB (NF-κB) signaling molecules were detected by western blot analysis. Detection of p65 nuclear translocation of NF-κB was examined using immunofluorescence staining. The OA rats received intraperitoneal injections of α-MG (10mg/kg) or saline every other day. Hematoxylin and eosin and Safranin-O-Fast green staining were used to evaluate the severity of cartilage lesions up to 8weeks following surgery. α-MG inhibited the production of NO and PGE2. The elevated expression of INOS, COX-2, MMP-3, MMP-9, and MMP-13, and the degradation of Collagen II and Aggrecan, were reversed by α-MG in IL-1ß-stimulated chondrocytes. In addition, IL-1ß induced considerable phosphorylation of the NF-kB signaling pathway, which was inhibited by α-MG. Furthermore, the immunofluorescence staining demonstrated that α-MG could suppress IL-1ß-induced p65 nuclear translocation. In vivo, cartilage treated with α-MG showed attenuated degeneration and had low Osteoarthritis Research Society International (OARSI) scores compared with the control group. Taken together, these results show that α-MG has potential therapeutic value in the treatment of OA.
Assuntos
Anti-Inflamatórios/uso terapêutico , Condrócitos/imunologia , Inflamação/tratamento farmacológico , Osteoartrite/tratamento farmacológico , Xantonas/uso terapêutico , Animais , Células Cultivadas , Ciclo-Oxigenase 2/metabolismo , Dinoprostona/metabolismo , Modelos Animais de Doenças , Garcinia mangostana/imunologia , Humanos , Interleucina-1beta/metabolismo , Masculino , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Meniscos Tibiais/cirurgia , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de SinaisRESUMO
Osteoarthritis (OA) is a chronic degenerative joint disease that is characterized by progressive joint dysfunction and pain. Apoptosis and catabolism in chondrocytes play critical roles in the development of OA. Alpha-Mangostin (α-MG), one of the main components of the mangosteen, has been reported to have anti-apoptotic, anti-inflammatory and antioxidant effects. We investigated the therapeutic effects of α-MG on OA through experiments on rat chondrocytes in vitro and in a rat model of OA induced by destabilization of the medial meniscus (DMM). In vitro, we provided experimental evidence that α-MG inhibits the expression of MMP-13 and ADAMTs-5, and promotes the expression of SOX-9 in rat chondrocytes stimulated with interleukin-1ß (IL-1ß). In addition, we also found that α-MG can inhibit the expression of pro-apoptotic proteins such as Bax, Cyto-c, and C-caspase3, and increase the expression of the anti-apoptotic protein Bcl-2. These changes may be related to an α-MG induced inhibition of the IL-1ß-induced activation of the NF-kB signaling pathway. In vivo, we also found that α-MG can limit the development of OA in rat models. The above results show that α-MG has a potential therapeutic effect on OA, and that this effect may be achieved by inhibiting the mitochondrial apoptosis of chondrocytes induced by an activation of the NF-kB pathway.