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1.
PLoS One ; 15(4): e0231240, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32287299

RESUMO

OBJECTIVE: REG-O3 is a 24-aminoacid chimeric peptide combining a sequence derived from growth hormone (GH) and an analog of somatostatin (SST), molecules displaying cartilage repair and anti-inflammatory properties, respectively. This study aimed to investigate the disease-modifying osteoarthritis drug (DMOAD) potential of REG-O3 by analyzing its effect on pain, joint function and structure, upon injection into osteoarthritic rat knee joint. DESIGN: Osteoarthritis was induced in the right knee of mature male Lewis rats (n = 12/group) by surgical transection of the anterior cruciate ligament (ACLT) combined with partial medial meniscectomy (pMMx). Treatments were administered intra-articularly from fourteen days after surgery through three consecutive injections one week apart. The effect of REG-O3, solubilized in a liposomal solution and injected at either 5, 25 or 50 µg/50 µL, was compared to liposomal (LIP), dexamethasone and hyaluronic acid (HA) solutions. The study endpoints were the pain/function measured once a week throughout the entire study, and the joint structure evaluated eight weeks after surgery using OARSI score. RESULTS: ACLT/pMMx surgery induced a significant modification of weight bearing in all groups. When compared to liposomal solution, REG-O3 was able to significantly improve weight bearing as efficiently as dexamethasone and HA. REG-O3 (25 µg) was also able to significantly decrease OARSI histological global score as well as degeneration of both cartilage and matrix while the other treatments did not. CONCLUSION: This study provides evidence of a remarkable protecting effect of REG-O3 on pain/knee joint function and cartilage/matrix degradation in ACLT/pMMx model of rat osteoarthritis. REG-O3 thus displays an interesting profile as a DMOAD.


Assuntos
Lesões do Ligamento Cruzado Anterior/complicações , Anti-Inflamatórios não Esteroides/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Hormônio do Crescimento/uso terapêutico , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Proteínas Recombinantes de Fusão/uso terapêutico , Somatostatina/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Cartilagem Articular/patologia , Modelos Animais de Doenças , Hormônio do Crescimento/farmacologia , Articulação do Joelho/patologia , Masculino , Osteoartrite do Joelho/etiologia , Ratos , Ratos Endogâmicos Lew , Proteínas Recombinantes de Fusão/farmacologia , Somatostatina/análogos & derivados , Somatostatina/farmacologia
2.
Int J Nanomedicine ; 15: 2379-2390, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308389

RESUMO

Background: Osteoarthritis (OA) is the most common type of joint disease associated with cartilage breakdown. However, the role played by mitochondrial dysfunction in OA remains inadequately understood. Therefore, we investigated the role played by p66shc during oxidative damage and mitochondrial dysfunction in OA and the effects of p66shc downregulation on OA progression. Methods: Monosodium iodoacetate (MIA), which is commonly used to generate OA animal models, inhibits glycolysis and biosynthetic processes in chondrocytes, eventually causing cell death. To observe the effects of MIA and poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles, histological analysis, immunohistochemistry, micro-CT, mechanical paw withdrawal thresholds, quantitative PCR, and measurement of oxygen consumption rate and extracellular acidification rate were conducted. Results: p-p66shc was highly expressed in cartilage from OA patients and rats with MIA-induced OA. MIA caused mitochondrial dysfunction and reactive oxygen species (ROS) production, and the inhibition of p66shc phosphorylation attenuated MIA-induced ROS production in human chondrocytes. Inhibition of p66shc by PLGA-based nanoparticles-delivered siRNA ameliorated pain behavior, cartilage damage, and inflammatory cytokine production in the knee joints of MIA-induced OA rats. Conclusion: p66shc is involved in cartilage degeneration in OA. By delivering p66shc-siRNA-loaded nanoparticles into the knee joints with OA, mitochondrial dysfunction-induced cartilage damage can be significantly decreased. Thus, p66shc siRNA PLGA nanoparticles may be a promising option for the treatment of OA.


Assuntos
Mitocôndrias/patologia , Osteoartrite/tratamento farmacológico , RNA Interferente Pequeno/farmacologia , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/genética , Proteína 1 de Transformação que Contém Domínio 2 de Homologia de Src/metabolismo , Animais , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Condrócitos/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Humanos , Ácido Iodoacético/toxicidade , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/efeitos dos fármacos , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Nanopartículas/administração & dosagem , Nanopartículas/química , Nanopartículas/uso terapêutico , Osteoartrite/induzido quimicamente , Osteoartrite/patologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , RNA Interferente Pequeno/administração & dosagem , Ratos Sprague-Dawley
3.
Pain Physician ; 23(2): E151-E161, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32214292

RESUMO

BACKGROUND: Ginger has been proposed as a complementary treatment for musculoskeletal pain. However, efficacy, type, and safety remains unclear. OBJECTIVES: To determine the effectiveness of consumption or topical application of ginger for pain relief and knee function improvement in patients with knee osteoarthritis. STUDY DESIGN: Systematic review with meta-analysis of randomized clinical trials. METHODS: An electronic search was performed on Medline, Central, CINAHL, PEDro, SPORTDiscus, and LILACS databases. The eligibility criteria for selecting studies included clinical trials that compared consumption and/or topical ginger with placebo or other interventions for the pain relief and knee function in patients with medical diagnosis of knee osteoarthritis. RESULTS: Seven clinical trials met the eligibility criteria, and for the quantitative synthesis, 4 studies were included. For the comparison capsules versus placebo, mean difference for pain was -7.88 mm; 95% confidence interval (CI), 11.92 to 3.85 (P = 0.00), and standard mean difference for knee function was -1.61 points; 95% CI, -4.30 to -1.09 (P = 0.24). For the comparison of topical ginger versus standard treatment, standard mean difference for pain was 0.79 mm; 95% CI, -1.97 to 0.39 (P = 0.19), and standard mean difference for knee function was -0.51 points; 95% CI, -1.15 to 0.13 (P = 0.12). LIMITATIONS: The current evidence is heterogeneous and has a poor methodologic quality. CONCLUSIONS: There is insufficient evidence to support the use of oral ginger compared with placebo in the pain relief and function improvement in patients with knee osteoarthritis. For other comparisons, no statistically significant differences were found. KEY WORDS: Osteoarthritis, knee osteoarthritis, ginger, pain, randomized clinical trial, systematic review.


Assuntos
Gengibre , Osteoartrite do Joelho/tratamento farmacológico , Manejo da Dor/métodos , Extratos Vegetais/administração & dosagem , Recuperação de Função Fisiológica/efeitos dos fármacos , Humanos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/fisiologia , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/tratamento farmacológico , Dor Musculoesquelética/epidemiologia , Osteoartrite do Joelho/diagnóstico , Osteoartrite do Joelho/epidemiologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Extratos Vegetais/isolamento & purificação , Recuperação de Função Fisiológica/fisiologia
4.
PLoS One ; 15(3): e0230228, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32163510

RESUMO

This study was designed to evaluate the anti-inflammatory effects of a curcumin treatment on the knee of rats with induced osteoarthritis. Fifteen adult rats were used and divided in three groups: the osteoarthritis group (OAG), control group (CG-without induction of osteoarthritis), and curcumin-treated osteoarthritis group (COAG). Osteoarthritis was induced in the right knee of rats in the OAG and COAG by administering an intra-articular injection of 1 mg of zymosan. Fourteen days after induction, 50 mg/kg curcumin was administered by gavage daily for 60 days to the COAG. After the treatment period, rats from all groups were euthanized. Medial femoral condyles were collected for light microscopy and immunohistochemical staining. The expression of SOX-5, IHH, MMP-8, MMP-13, and collagen 2 (Col2) was analyzed. The COAG exhibited an increase in the number of chondrocytes in the surface and middle layers compared with that of the OAG and CG, respectively. The COAG also showed a decrease in the thicknesses of the middle and deep layers compared with those of the OAG, and an increase in Col2 expression was observed in all articular layers (surface, middle, and deep) in the COAG compared with that in the OAG. SOX-5 expression was increased in the surface and deep layers of the COAG compared with those in the OAG and CG. Based on the results of this study, the curcumin treatment appeared to exert a protective effect on cartilage, as it did not result in an increase in cartilage thickness or in MMP-8 and MMP-13 expression but led to increased IHH, Col2, and SOX-5 expression and the number of chondrocytes.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Curcumina/farmacologia , Articulação do Joelho/efeitos dos fármacos , Osteoartrite/tratamento farmacológico , Animais , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Colágeno Tipo II/metabolismo , Injeções Intra-Articulares/métodos , Articulação do Joelho/metabolismo , Masculino , Osteoartrite/metabolismo , Ratos , Ratos Wistar
5.
Medicine (Baltimore) ; 99(8): e18912, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32080074

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is the most common form of degenerative arthritis. We used Phellinus linteus (PL), which has been well-known anti-inflammatory function. In this study, we will evaluate if PL extract improves symptoms with KOA. METHODS: This study will be an 8-week single-center randomized controlled double-blind clinical trial. Total of 24 subjects with KOA will be enrolled and they will be divided into 3 groups, PL 1,000 mg, PL 1,500 mg and placebo. Subjects will be followed up every 4 weeks with efficacy and safety at the 2nd and 3rd visits. All subjects should maintain a dosage schedule for this protocol. The primary outcome will be assessed with the Korean version of the Western Ontario and McMasters Universities. And the secondary outcomes will be measured using the visual analog scale, quality of life scale (EQ-5D-3L), ESR, C-reactive protein, and C-telopeptide of type-II collagen. Statistical analysis will be performed on the principle of full analysis set. DISCUSSION: This study has inclusion and exclusion criteria and a well-controlled intervention. This clinical trial is the first step to assess the efficacy and safety of PL in patients with KOA. This study will make an important contribution to the literature and aid follow-up research into the use of PL in KOA.


Assuntos
Cartilagem Articular/efeitos dos fármacos , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Administração Oral , Adulto , Idoso , Sedimentação Sanguínea/efeitos dos fármacos , Proteína C-Reativa/efeitos dos fármacos , Colágeno Tipo I/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/sangue , Osteoartrite do Joelho/patologia , Peptídeos/efeitos dos fármacos , Placebos/administração & dosagem , Extratos Vegetais/uso terapêutico , Estudos Prospectivos , Qualidade de Vida , República da Coreia/epidemiologia , Resultado do Tratamento
6.
J Ethnopharmacol ; 248: 112277, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31606533

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Knee osteoarthritis (OA) cause pain and edema, as well as unbalance between the production of reactive oxygen species and antioxidant activity. These problems interfere with the articular function, leading to a significant loss of life quality. Sida tuberculata R.E.Fr. is an herbaceous plant belonging to the Malvaceae family found in southern Brazil. This plant has traditionally been consumed as an aqueous extract and popularly used in the treatment of many diseases, with antioxidant and antimicrobial activity, reducing pain and inflammation. AIM OF THE STUDY: To verify the effects of S. tuberculata extract obtained from leaves on oxidative, toxic and nociceptive parameters induced by knee OA in rats. MATERIALS AND METHODS: Aqueous extracts of S. tuberculata were evaluated under phytochemical analyses. Knee Osteoarthritis was induced in rats with monosodium iodoacetate (1.5 mg/50 µl) and treated with S. tuberculata extract. The animals were treated orally with 3 doses of S. tuberculata extract (STE): 1.5, 5 and 15 mg/ml, for 14 days. For biochemical analyses, the following tests were performed: lipid peroxidation, carbonylated protein content, superoxide dismutase activity, non-protein thiol levels and myeloperoxidase activity. For the evaluation of pain and edema we verify mechanical and thermal hyperalgesia, spontaneous pain observation and measurement of knee edema with a caliper. For histological evaluations, the animal knee joints were removed. For toxicity evaluation, the levels of aspartate aminotransferase, alanine aminotransferase and urea, as well as the relative weight of the organs were analyzed. RESULTS: The S. tuberculata phytochemical analyses showed the majority peak corresponding to 20-hydroxyecdysone (20HE). The plant extract decreased damages related to oxidative stress in the blood serum (lipid peroxidation and carbonyl content) Overall, the STE 5 mg Group presented the greater statistical significance, in the blood serum samples, in relation to the other groups, being the most relevant result. The S. tuberculata groups presented pain decrease, lower neutrophil activity in the knee, and increased blood serum activity. The animals of S. tuberculata groups showed a decrease in mechanical hyperalgesia. The animals treated also presented lower scores for spontaneous pain. It was observed that the dose of 5 mg presented, once again, more expressive results, since the animals of this group had a higher frequency (greater number of days) with significant decrease of pain. In the histological analysis, in the STE 5 mg group, the articular cartilage lesions were observed at an intermediate point between the damage found in the MIA and Diclofenac groups. Besides that, the STE did not show significant changes in oxidative stress damage in liver and kidney samples. Blood serum samples did not indicate significant differences in liver and renal function. As well as, there were no differences in mean relative body weights in relation to control groups (Salina and MIA). CONCLUSION: S. tuberculata reduced the damage due to oxidative stress and pain caused by knee osteoarthritis in rats. In addition, the extract presented no toxicity. Our results suggest that S. tuberculata seems to have a therapeutic potential in the osteoarthritis treatment.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Malvaceae , Osteoartrite do Joelho/tratamento farmacológico , Dor/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Edema/tratamento farmacológico , Edema/metabolismo , Edema/patologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Estresse Oxidativo/efeitos dos fármacos , Dor/metabolismo , Peroxidase/metabolismo , Extratos Vegetais/farmacologia , Ratos Wistar , Superóxido Dismutase/metabolismo
7.
Arthritis Res Ther ; 21(1): 292, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31847895

RESUMO

OBJECTIVES: To examine the ability of takinib, a selective transforming growth factor beta-activated kinase 1 (TAK1) inhibitor, to reduce the severity of murine type II collagen-induced arthritis (CIA), and to affect function of synovial cells. METHODS: Following the induction of CIA, mice were treated daily with takinib (50 mg/kg) and clinical scores assessed. Thirty-six days post-CIA induction, histology was performed on various joints of treated and vehicle-treated animals. Inflammation, pannus, cartilage damage, bone resorption, and periosteal bone formation were quantified. Furthermore, pharmacokinetics of takinib were evaluated by LC-MS in various tissues. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) cells were cultured with 10 µM takinib and cytokine secretion analyzed by cytokine/chemokine proteome array. Cytotoxicity of takinib for RA-FLS was measured with 24 to 48 h cultures in the presence or absence of tumor necrosis factor (TNF). RESULTS: Here, we show takinib's ability to reduce the clinical score in the CIA mouse model of rheumatoid arthritis (RA) (p < 0.001). TAK1 inhibition reduced inflammation (p < 0.01), cartilage damage (p < 0.01), pannus, bone resorption, and periosteal bone formation and periosteal bone width in all joints of treated mice compared to vehicle treated. Significant reduction of inflammation (p < 0.004) and cartilage damage (p < 0.004) were observed in the knees of diseased treated animals, with moderate reduction seen in the forepaws and hind paws. Furthermore, the pharmacokinetics of takinib show rapid plasma clearance (t½ = 21 min). In stimulated RA-FLS cells, takinib reduced GROα, G-CSF, and ICAM-1 pro-inflammatory cytokine signaling. CONCLUSION: Our findings support the hypothesis that TAK1 targeted therapy represents a novel therapeutic axis to treat RA and other inflammatory diseases.


Assuntos
Artrite Experimental/prevenção & controle , Benzamidas/farmacologia , Benzimidazóis/farmacologia , MAP Quinase Quinase Quinases/antagonistas & inibidores , Sinoviócitos/efeitos dos fármacos , Animais , Artrite Experimental/metabolismo , Artrite Experimental/patologia , Artrite Reumatoide/metabolismo , Artrite Reumatoide/patologia , Artrite Reumatoide/prevenção & controle , Benzamidas/farmacocinética , Benzimidazóis/farmacocinética , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Inflamação/metabolismo , Inflamação/prevenção & controle , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , MAP Quinase Quinase Quinases/metabolismo , Camundongos Endogâmicos DBA , Inibidores de Proteínas Quinases/farmacologia , Índice de Gravidade de Doença , Sinoviócitos/metabolismo
8.
Biomed Res Int ; 2019: 4575424, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781616

RESUMO

Background: Upper partial fibulectomy has been preliminarily proved to have the efficacy for pain alleviation and improvement of function in patients with mild to moderate medial compartment knee osteoarthritis (KOA). However, the previous studies lack the control group with other treatments. The aim of this prospective, randomized controlled study is to compare the clinical and biomechanical effects between upper partial fibulectomy and drug conservative treatment on improvement of clinical pain, function, and gait for patients with mild to moderate medial knee osteoarthritis (KOA) and further discuss its biomechanical mechanism. Methods: From August 2016 to February 2017, 49 and 48 patients with mild to moderate medial KOA were allocated to fibulectomy and drug groups. We assessed the patients' visual analog scale (VAS) pain score, Hospital for Special Surgery (HSS) knee score, limb alignment, passive flexion/extension range of motion (ROM) of the knee, and 3D gait kinematics and kinetics parameters before and after intervention. Repeated-measures ANOVA with Dunnett's post hoc assessment and multivariate analysis of variance were applied for intragroup and intergroup comparisons, respectively. Results: The improvement in the fibulectomy group on the VAS pain score, HSS knee score, walking speed, and walking knee range of motion (ROM) was statistically better than that in the drug group. The decreased overall peak knee adduction moment (KAM) (decreased by 16.1%) and hip-knee-ankle (HKA) angle (decreased by 0.99° from a more varus alignment to a more neutral alignment) of the affected and operated side 1 year after surgery were observed in the fibulectomy group. Conclusion: This research demonstrated that as a biomechanical intervention, upper partial fibulectomy can be a better choice in pain relief and function and gait improvement than drug conservative treatment for patients with early-stage knee OA. The long-term clinical outcomes, indication, and rationale for the improvement in clinical symptoms should be investigated further.


Assuntos
Articulação do Joelho/cirurgia , Ligamento Colateral Médio do Joelho/cirurgia , Osteoartrite do Joelho/tratamento farmacológico , Osteoartrite do Joelho/cirurgia , Idoso , Fenômenos Biomecânicos/efeitos dos fármacos , Fenômenos Biomecânicos/fisiologia , Tratamento Conservador , Feminino , Marcha/fisiologia , Humanos , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/fisiopatologia , Masculino , Ligamento Colateral Médio do Joelho/efeitos dos fármacos , Ligamento Colateral Médio do Joelho/fisiopatologia , Pessoa de Meia-Idade , Osteoartrite do Joelho/fisiopatologia , Amplitude de Movimento Articular/efeitos dos fármacos , Tíbia/efeitos dos fármacos , Tíbia/fisiopatologia , Tíbia/cirurgia , Resultado do Tratamento , Caminhada
9.
Int Immunopharmacol ; 77: 105928, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31711940

RESUMO

Osteoarthritis (OA), a common and severe disease, is predominantly characterized by cartilage destruction, which results in the degeneration of joint surfaces. Nowadays, it is accepted that TNFα plays a critical role in OA. Scutellarin, the main bioactive flavonoid glycoside extracted form Erigeron breviscapus, has been reported to exert positive effects on anti-inflammatory reactions. However, the effect of scutellarin in OA is still unknown. In this study, we isolated and cultured primary murine chondrocytes, stimulating TNF-α, in the presence or absence of scutellarin treatment. We found that the inflammatory response stimulated by TNF-α was significantly inhibited by the addition of scutellarin. Moreover, we established OA mouse models induced by surgery. In this mouse model, both inflammatory reaction and cartilage degeneration were markedly inhibited by oral administration of scutellarin. Furthermore, the cellular mechanism underlying the protective effect of scutellarin in OA was clearly associated with the NF-κB and PI3K/AKT signaling pathways. Collectively, this study proposes scutellarin as a potential therapeutic to treat joint degenerative diseases, including OA.


Assuntos
Anti-Inflamatórios/uso terapêutico , Apigenina/uso terapêutico , Cartilagem/efeitos dos fármacos , Glucuronatos/uso terapêutico , NF-kappa B/metabolismo , Osteoartrite/tratamento farmacológico , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Apigenina/farmacologia , Cartilagem/metabolismo , Cartilagem/patologia , Glucuronatos/farmacologia , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Camundongos Endogâmicos C57BL , NF-kappa B/genética , Osteoartrite/metabolismo , Osteoartrite/patologia , Transdução de Sinais/efeitos dos fármacos
10.
Biomed Res Int ; 2019: 4040236, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31687388

RESUMO

Osteochondral lesions (OCs) are typically of traumatic origins but are also caused by degenerative conditions, in primis osteoarthritis (OA). On the other side, OC lesions themselves, getting worse over time, can lead to OA, indicating that chondral and OC defects represent a risk factor for the onset of the pathology. Many animal models have been set up for years for the study of OC regeneration, being successfully employed to test different treatment strategies, from biomaterials and cells to physical and biological adjuvant therapies. These studies rely on a plethora of post-explant investigations ranging from histological and histomorphometric analyses to biomechanical ones. The present review aims to analyze the methods employed for the evaluation of OC treatments in each animal model by screening literature data within the last 10 years. According to the selected research criteria performed in two databases, 60 works were included. Data revealed that lapine (50% of studies) and ovine (23% of studies) models are predominant, and knee joints are the most used anatomical locations for creating OC defects. Analyses are mostly conducted on paraffin-embedded samples in order to perform histological/histomorphometric analyses by applying semiquantitative scoring systems and on fresh samples in order to perform biomechanical investigations by indentation tests on articular cartilage. Instead, a great heterogeneity is pointed out in terms of OC defect dimensions and animal's age. The choice of experimental times is generally adequate for the animal models adopted, although few studies adopt very long experimental times. Improvements in data reporting and in standardization of protocols would be desirable for a better comparison of results and for ethical reasons related to appropriate and successful animal experimentation.


Assuntos
Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Animais , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Humanos , Traumatismos do Joelho/tratamento farmacológico , Traumatismos do Joelho/patologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Modelos Animais
11.
Medicine (Baltimore) ; 98(39): e17386, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31574892

RESUMO

INTRODUCTION: The purpose of this study was to use meta-analysis techniques to evaluate the efficacy and safety of polydeoxyribonucleotide (PDRN) injections for knee osteoarthritis (OA) treatment. METHODS: Multiple comprehensive databases, including MEDLINE, EMBASE, and the Cochrane Library, were searched in November 2018 for studies that compared the effectiveness and safety of intra-articular PDRN injection for the knee joint with hyaluronic acid (HA) injection. Two reviewers independently determined study inclusion and they extracted data using a standardized data extraction form. The predefined primary outcome was Visual Analogue Scale. Secondary outcomes included Knee Injury and Osteoarthritis Outcome Score (KOOS), Knee Society Score (KSS), and adverse events. RESULTS: Five randomized controlled trials were included in the meta-analysis. After 1 and 2 months, patients in the PDRN group showed significantly better improvement in pain than the HA group (P = .04 and P = .02, respectively). There was no significant difference in pain after 4 months. The pooled analysis showed that no significant differences were seen in function (KOOS and KSS) scores between the PDRN and HA groups (all P > .05) at all time points. There was no significant difference in adverse events between 2 groups (relative risks = 2.15, 95% confidential interval: 0.17-26.67, P = .55). CONCLUSION: The intra-articular use of PDRN was similar in function to HA, and the pain-relief effect was superior to HA for 2 months post-injection. Therefore, it could be a favorable alternative to HA to treat persistent pain associated with knee OA while avoiding side effects.Level of evidence I.


Assuntos
Ácido Hialurônico/administração & dosagem , Osteoartrite do Joelho/tratamento farmacológico , Polidesoxirribonucleotídeos/administração & dosagem , Viscossuplementos/administração & dosagem , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
12.
Nutrients ; 11(9)2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31470599

RESUMO

Osteoarthritis (OA) is the most common form of arthritis in the world and is characterized by pain, various disabilities and loss of quality of life. Chondroitin sulfate (CS) is recommended as first-line therapy. CS of non-animal origin is of great interest for safety and sustainability reasons. This study aims to investigate the anti-inflammatory effects, anti-pain and ability-enhancement of a short-term supplementation with non-animal CS in overweight subjects with OA. In a randomized, double-blind, placebo-controlled pilot study, 60 overweight adults with symptomatic OA were allocated to consume 600 mg of non-animal CS (n = 30) or a placebo (n = 30) daily for 12 consecutive weeks. The assessment of knee-pain, quality of life, related inflammation markers and body composition was performed at 0, 4 and 12 weeks. The Tegner Lysholm Knee Scoring (TLKS) scale of the experimental group showed a statistically significant increase (+10.64 points; confidence interval (95% confidence interval (CI) 5.57; 15.70; p < 0.01), while the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score decreased (-12.24 points; CI 95% -16.01; -8.38; p < 0.01). The results also showed a decrease in the C-reactive protein (CRP) level (-0.14 mg/dL, CI 95% -0.26; -0.04; p < 0.01) and erythrocyte sedimentation rate (ESR) level (-5.01 mm/h, CI 95% -9.18; -0.84, p < 0.01) as well as the visual analogue scale (VAS) score in both knees. In conclusion, this pilot study demonstrates the effectiveness of non-animal CS supplementation in overweight subjects with knee OA in improving knee function, pain and inflammation markers.


Assuntos
Anti-Inflamatórios/uso terapêutico , Sulfatos de Condroitina/uso terapêutico , Suplementos Nutricionais , Articulação do Joelho/efeitos dos fármacos , Osteoartrite do Joelho/tratamento farmacológico , Sobrepeso/complicações , Absorciometria de Fóton , Adiposidade , Idoso , Anti-Inflamatórios/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Sulfatos de Condroitina/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Mediadores da Inflamação/sangue , Itália , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/fisiopatologia , Sobrepeso/diagnóstico por imagem , Sobrepeso/fisiopatologia , Medição da Dor , Projetos Piloto , Qualidade de Vida , Recuperação de Função Fisiológica , Fatores de Tempo , Resultado do Tratamento
13.
BMC Musculoskelet Disord ; 20(1): 424, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31511072

RESUMO

BACKGROUND: Intra-articular (IA) injection of hyaluronic acid (HA) (IA-HA) is a well-recognized treatment option for pain associated with symptomatic knee osteoarthritis (OA). IA-HA products differ in their HA content, molecular weight, cross-linking, and source of HA. These differences are assumed to affect the biocompatibility of the IA-HA products once injected inside the knee joint. METHODS: In the present study, we investigated the biocompatibility of three multiple-injection IA-HA products available in the global market. These included SUPARTZ FX™, a medium range molecular weight HA derived from rooster comb (Avian-HA); ORTHOVISC®, a high range molecular weight HA obtained through biological fermentation (Bio-HA); and SYNVISC®, a high molecular weight cross-linked hyaluronan derived from rooster comb (Avian-CL-HA). Rabbit knee joint tissues were histologically and biochemically examined after IA injection of the products. Furthermore, we compared the amounts of impurities in the IA-HA products. RESULTS: IA injection of Avian-CL-HA into rabbit knee joints induced the aggregation of inflammatory cells, infiltration of eosinophils, and an increase in the number of cells in the synovial fluid. However, these effects were not seen in the Avian-HA and Bio-HA groups. The residual protein content and the contaminant levels of bacterial endotoxins were below the limit of quantitation in all HA products. Avian-CL-HA contained relatively a large amount of (1 → 3)-ß-D-glucan, but this was below the lower limit of quantification in the other HA products. CONCLUSIONS: The present results clearly demonstrate that the biocompatibility of Avian-HA is comparable to that of Bio-HA, and they were both considered to have a favorable safety profile for the treatment of symptomatic OA of the knee. However, immunostimulatory activity was observed after injection of Avian-CL-HA: this might be a result of its unique cross-linking structure and/or the considerable amount of (1 → 3)-ß-D-glucan impurity present in the formulation.


Assuntos
Ácido Hialurônico/análogos & derivados , Viscossuplementos/administração & dosagem , Animais , Contaminação de Medicamentos , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Injeções Intra-Articulares , Articulação do Joelho/efeitos dos fármacos , Masculino , Teste de Materiais , Modelos Animais , Osteoartrite do Joelho/tratamento farmacológico , Coelhos , Líquido Sinovial/citologia , Líquido Sinovial/efeitos dos fármacos , Viscossuplementos/efeitos adversos
14.
Drug Des Devel Ther ; 13: 2603-2618, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440039

RESUMO

Background: After a trauma, exuberant tissue healing with fibrosis of the joint capsule can lead to posttraumatic joint stiffness (PTJS). Losartan and atorvastatin have both shown their antifibrotic effects in different organ systems. Objective: The purpose of this study was the evaluation of the influence of losartan and atorvastatin on the early development of joint contracture. In addition to joint angles, the change in myofibroblast numbers and the distribution of bone sialoprotein (BSP) were assessed. Study design and methods: In this randomized and blinded experimental study with 24 rats, losartan and atorvastatin were compared to a placebo. After an initial joint injury, rat knees were immobilized with a Kirschner wire. Rats received either losartan, atorvastatin or a placebo orally daily. After 14 days, joint angle measurements and histological assessments were performed. Results: Losartan increased the length of the inferior joint capsule. Joint angle and other capsule length measurements did not reveal significant differences between both drugs and the placebo. At cellular level both losartan and atorvastatin reduced the total number of myofibroblasts (losartan: 191±77, atorvastatin: 98±58, placebo: 319±113 per counting field, p<0.01) and the percentage area of myofibroblasts (losartan: 2.8±1.8% [p<0.05], atorvastatin: 2.5±1.7% [p<0.01], vs control [6.4±4%], respectively). BSP was detectable in equivalent amounts in the joint capsules of all groups with only a trend toward a reduction of the BSP-stained area by atorvastatin. Conclusion: Both atorvastatin and losartan reduced the number of myofibroblasts in the posterior knee joint capsule of rat knees 2 weeks after trauma and losartan increased the length of the inferior joint capsule. However, these changes at the cellular level did not translate an increase in range of motion of the rats´ knee joints during early contracture development.


Assuntos
Atorvastatina/farmacologia , Cápsula Articular/efeitos dos fármacos , Traumatismos do Joelho/tratamento farmacológico , Articulação do Joelho/efeitos dos fármacos , Losartan/farmacologia , Animais , Atorvastatina/administração & dosagem , Modelos Animais de Doenças , Fibrose/tratamento farmacológico , Fibrose/patologia , Cápsula Articular/patologia , Traumatismos do Joelho/patologia , Articulação do Joelho/patologia , Losartan/administração & dosagem , Masculino , Ratos , Ratos Sprague-Dawley
15.
BMC Complement Altern Med ; 19(1): 191, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31362725

RESUMO

BACKGROUND: Wnt/ß-catenin signaling pathway is closely related to osteoarthritis. In our preliminary study, ß-catenin conditional activation (cAct) mice that specifically over-express ß-catenin gene in cartilage chondrocyte exhibits osteoarthritis-like phenotype in the lumbar disc and knee joint. Therefore, we used the mice to model FJ-OA and test the potential curative effect of Velvet Antler Polypeptide (VAP) on this mice model. METHODS: We tested the effect of VAP on ß-catenin conditional activation mice, and used Cre negative littermates as controls. Micro-CT, histology and histomorphometry analysis were performed to evaluate the curative effect of VAP on mice facet joint-like phenotype. Expression of ß-catenin and collagen II was detected by immunohistochemistry (IHC) and western-blot., MMP13, ADAMTS4 and ADAMTS5 was detected by immunofluorescence (IF). RT-PCR analysis was preformed to detect mRNA expression of cartilage degrading enzymes, such as MMP13, ADAMTS4 and ADAMTS5. RESULTS: Results of micro-CT (µCT) analysis showed that VAP could partially reverse lumbar disc osteophyte formation observed in ß-catenin(ex3)Col2ER mice. Histology data revealed VAP partially improved facet joint cartilage tissue invades. Histomorphometry analysis showed an increase in total cartilage area after VAP treatment. IHC show that VAP reduced ß-catenin protein levels and moderately up-regulated collagen II protein levels. RT-PCR and IF data showed that VAP down-regulated the expression of extracellular matrix synthesis (ECM) degradation enzymes MMP13, ADAMTS4 and ADAMTS5. CONCLUSION: Taken together, VAP may modulate ECM by inhibits MMP13, ADAMTS4 and ADAMTS5 via Wnt /ß-catenin signaling pathway. Velvet Antler Polypeptide may be a potential medicine for FJ-OA.


Assuntos
Chifres de Veado/química , Osteoartrite/tratamento farmacológico , Peptídeos/administração & dosagem , beta Catenina/metabolismo , Proteína ADAMTS4/genética , Proteína ADAMTS4/metabolismo , Proteína ADAMTS5/genética , Proteína ADAMTS5/metabolismo , Animais , Apoptose/efeitos dos fármacos , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/metabolismo , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Cervos , Humanos , Articulações/efeitos dos fármacos , Articulação do Joelho/efeitos dos fármacos , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Camundongos , Osteoartrite/genética , Osteoartrite/metabolismo , beta Catenina/genética
16.
Cells ; 8(8)2019 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-31382623

RESUMO

One option to fight joint degradation and inflammation in osteoarthritis is the injection of activated blood products into the synovial space. It has been demonstrated that hyperacute serum is the most proliferative among plasma products, so we investigated how the cytokine milieu of osteoarthritic knee joint reacts to hyperacute serum treatment in vitro. Cartilage, subchondral bone, and synovial membrane explanted from osteoarthritic knees were stimulated by interleukin-1 beta (IL-1ß) and the concentration of 39 biomarkers was measured in the co-culture supernatant after hyperacute serum treatment. The IL-1ß stimulation triggered a strong inflammatory response and enhanced the concentrations of matrix metalloproteinase 3 and 13 (MMP-3 and MMP-13), while hyperacute serum treatment reduced inflammation by decreasing the concentrations of IL-1ß, tumor necrosis factor alpha (TNF-α), interleukin-6 receptor alpha (IL-6Rα), and by increasing the level of interleukin-1 antagonist (IL-1RA) Cell viability increased by day 5 in the presence of hyperacute serum. The level of MMPs-1, 2, and 9 were higher on day 3, but did not increase further until day 5. The concentrations of collagen 1 alpha 1 (COL1A1) and osteonectin were increased and receptor activator of nuclear factor kappa-B ligand (RANKL) was reduced in response to hyperacute serum. We concluded that hyperacute serum treatment induces cell proliferation of osteoarthritic joint tissues and affects the cytokine milieu towards a less inflamed state.


Assuntos
Citocinas/metabolismo , Interleucina-1beta/farmacologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/metabolismo , Osteoartrite do Joelho/terapia , Adulto , Cartilagem/efeitos dos fármacos , Cartilagem/patologia , Técnicas de Cocultura , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Membrana Sinovial/efeitos dos fármacos , Técnicas de Cultura de Tecidos , Adulto Jovem
17.
Int J Pharm ; 569: 118598, 2019 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-31394185

RESUMO

Topical nonsteroidal anti-inflammatory drugs have been used in treatment of osteoarthritis but their efficacy is marginal. One major reason is because of limited drug direct penetration to affected joint and muscle tissues from the topical application. The main purpose of this study was to evaluate a new topical treatment through enhancing the direct drug penetration to local muscle and joint tissues for improving topical treatment of osteoarthritis. A cationic prodrug, ketoprofen choline chloride (KCC) was synthesized for iontophoretic topical delivery. Anodal iontophoretic delivery of KCC and cathodal iontophoretic delivery of ketoprofen to the knee of live hairless rats were evaluated and the drug concentrations in the joint and muscle tissues over the time were determined. In addition, a knee osteoarthritis rat model was induced with intra-articular injection of monosodium iodoacetate solution. Anodal iontophoretic delivery of KCC, cathodal iontophoretic delivery of ketoprofen, or anodal iontophoretic delivery of sodium chloride were applied to the affected knee joint of each rat group, respectively. Knee joint pain was evaluated through a hind paw weight bearing study and knee joint inflammation was evaluated through measuring of the knee diameter. Iontophoretic delivery of KCC showed much higher drug concentration in the knee joint and muscle tissues, compared to iontophoretic delivery of ketoprofen. Treatment of rat knee joint with anodal iontophoresis of KCC also showed significant pain relief and knee inflammation reduction comparing to the control group, while treatment results from cathodal iontophoresis of ketoprofen were mostly not significantly different from the control group.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Iontoforese , Cetoprofeno/administração & dosagem , Osteoartrite/tratamento farmacológico , Dor/tratamento farmacológico , Animais , Modelos Animais de Doenças , Feminino , Iodoacetatos , Articulação do Joelho/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Osteoartrite/induzido quimicamente , Dor/induzido quimicamente , Ratos , Ratos Pelados
18.
Int Immunopharmacol ; 75: 105813, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31404889

RESUMO

Our previous studies demonstrated that oral administration of madecassoside could markedly attenuate collagen-induced arthritis in rats, a rodent model of rheumatoid arthritis. As the autonomic nervous system is critically involved in the modulation of peripheral inflammation and immune response, the present study aims to explore the possible involvement of adrenergic and cholinergic nerves in the effect of madecassoside on rheumatoid arthritis. Arthritis was induced by chicken collagen in rats, and madecassoside was orally administered daily for two weeks from day 14 after the primary immunization. The antagonists of adrenoceptor and cholinergic receptors were co-administered with madecassoside, respectively. Unilateral cervical vagotomy was performed four days before the arthritis induction. The results showed that madecassoside (30 mg/kg) treatment markedly ameliorated arthritis symptoms in rats, mainly evidenced by the reduction of paw swelling and arthritis index scores. Co-administration of madecassoside with atropine (an antagonist of the muscarinic acetylcholine receptor) or hexamethonium (an antagonist of the nicotinic acetylcholine receptor) markedly diminished the therapeutic effects of madecassoside in arthritis. However, co-administration with phentolamine (an antagonist of the α-adrenoceptor) or propranolol (an antagonist of the ß-adrenoceptor) did not alter the effect of madecassoside on arthritis. Furthermore, unilateral cervical vagotomy significantly reduced the anti-arthritis efficacy of madecassoside, including the amelioration of clinical symptoms, as well as the inhibition of the production of pro-inflammatory cytokines except T lymphocytes-related cytokines. These findings suggest that madecassoside exerts inhibitory effects on collagen-induced arthritis through, at least partially, the peripheral cholinergic system.


Assuntos
Anti-Inflamatórios/uso terapêutico , Artrite Experimental/tratamento farmacológico , Triterpenos/uso terapêutico , Nervo Vago , Administração Oral , Animais , Artrite Experimental/imunologia , Artrite Experimental/patologia , Citocinas/sangue , Citocinas/imunologia , Feminino , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Ratos Wistar , Vagotomia
19.
Int J Med Sci ; 16(6): 845-853, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31337958

RESUMO

Background: Knee joint pain is the most common reason for physical disability which associates with age. TamaFlexTM (NXT15906F6) is a synergistic anti-inflammatory formulation which contains ethanol/aqueous extracts of Tamarindus indica seeds and ethanol extract of Curcuma longa rhizome. Methods: In a 90-day randomized, double-blind, placebo-controlled study, we evaluated efficacy of NXT15906F6 in relieving pain and improving joint function in non-arthritic adults. Ninety non-arthritic subjects who experienced knee pain and joint discomfort following a six-minute walk test (SMWT) and Stair climb test (SCT) participated in the present trial. Subjects received either 250 mg (n=30) or 400 mg (n=30) of NXT15906F6 or matched placebo (PL: n=30) daily for 90 days. Improvement from baseline six-minute walk distance (SMWD) in NXT15906F6 groups, compared with placebo (PL) was the primary outcome of the study. Results: At post-intervention, subjects in NXT15906F6-250 (p<0.001) and NXT15906F6-400 (p<0.0001) groups showed substantial improvements in mean changes of SMWD from baseline compared to placebo. The 250 mg and 400 mg NXT15906F6 groups also improved average walking speed from baseline by 0.08±0.07 m/s (p=0.0010) and 0.11±0.08 m/s (p<0.0001), respectively. The NXT15906F6 groups experienced significant improvement in SMWT performances as early as 14 days. NXT15906F6-supplemented participants showed a consistent benefit of pain relief and improved musculoskeletal functions, compared to placebo. Conclusion: NXT15906F6 provided substantial relief from knee pain after physical activity and improved joint function in non-arthritic adults. Study participants did not show any major adverse events, and they tolerated well this novel herbal formulation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Artralgia/tratamento farmacológico , Articulação do Joelho/efeitos dos fármacos , Extratos Vegetais/administração & dosagem , Tamarindus/química , Adulto , Anti-Inflamatórios/efeitos adversos , Artralgia/diagnóstico , Artralgia/etiologia , Curcuma/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Exercício Físico/fisiologia , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Placebos/administração & dosagem , Placebos/efeitos adversos , Extratos Vegetais/efeitos adversos , Rizoma/química , Sementes/química , Resultado do Tratamento , Teste de Caminhada
20.
Int Immunopharmacol ; 75: 105715, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31310911

RESUMO

Pathological changes, such as articular cartilage degeneration, destruction, and hyperosteogeny, are regarded as the main features of osteoarthritis (OA). Sinomenine (SIN) is a monomeric component purified from the plant Sinomenium acutum which has been found to have anti-inflammatory effects, however, the mechanism of action of SIN on OA is not clear. In this study, we evaluated whether SIN could regulate the inflammatory response induced by interleukin (IL)-1ß and improve outcomes in the instability model of OA (medial meniscus mice (DMM)) by acting on the Nrf2/HO-1 and NF-κ B signaling pathways in chondrocytes. From our experiments, which include Griess reaction, ELISA, Western blot, and immunofluorescence, we found that SIN not only down-regulated the expression of pro-inflammatory factors induced by IL-1ß, including; inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), nitricoxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6), but also decreased the production of IL-1ß-induced cartilage matrix catabolic enzymes including; ADAMTS-5 and MMPs, in mouse chondrocytes. In addition, the degradation of aggrecan and type II collagen protein in the extracellular matrix (ECM) stimulated by IL-1ß was reversed. Most importantly, we have revealed for the first time that in OA, SIN inhibited the inflammatory response and ECM degradation by activating the Nrf2/HO-1 signaling pathways and inhibiting NF-κB activity in mouse-cartilage cells. In in vivo experiments, SIN treatment helped to improve the cartilage destruction in OA model mice. In conclusion, this study has demonstrated that SIN inhibits the IL-1ß-induced inflammatory response and cartilage destruction by activating the Nrf2/HO-1 signaling pathway and inhibiting the NF-κB signaling pathway in mouse chondrocytes, suggesting a new use for SIN in the treatment of OA.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Heme Oxigenase-1/imunologia , Proteínas de Membrana/imunologia , Morfinanos/farmacologia , Fator 2 Relacionado a NF-E2/imunologia , NF-kappa B/imunologia , Osteoartrite/imunologia , Animais , Anti-Inflamatórios/uso terapêutico , Cartilagem Articular/citologia , Células Cultivadas , Condrócitos/imunologia , Articulação do Joelho/efeitos dos fármacos , Articulação do Joelho/patologia , Masculino , Camundongos Endogâmicos C57BL , Morfinanos/uso terapêutico , Fator 2 Relacionado a NF-E2/genética , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Transdução de Sinais/efeitos dos fármacos
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