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1.
Int J Mol Sci ; 22(5)2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33804447

RESUMO

Interleukin (IL)-1ß is an important pro-inflammatory cytokine in the progression of osteoarthritis (OA), which impairs mitochondrial function and induces the production of nitric oxide (NO) in chondrocytes. The aim was to investigate if blockade of NO production prevents IL-1ß-induced mitochondrial dysfunction in chondrocytes and whether cAMP and AMP-activated protein kinase (AMPK) affects NO production and mitochondrial function. Isolated human OA chondrocytes were stimulated with IL-1ß in combination with/without forskolin, L-NIL, AMPK activator or inhibitor. The release of NO, IL-6, PGE2, MMP3, and the expression of iNOS were measured by ELISA or Western blot. Parameters of mitochondrial respiration were measured using a seahorse analyzer. IL-1ß significantly induced NO release and mitochondrial dysfunction. Inhibition of iNOS by L-NIL prevented IL-1ß-induced NO release and mitochondrial dysfunction but not IL-1ß-induced release of IL-6, PGE2, and MMP3. Enhancement of cAMP by forskolin reduced IL-1ß-induced NO release and prevented IL-1ß-induced mitochondrial impairment. Activation of AMPK increased IL-1ß-induced NO production and the negative impact of IL-1ß on mitochondrial respiration, whereas inhibition of AMPK had the opposite effects. NO is critically involved in the IL-1ß-induced impairment of mitochondrial respiration in human OA chondrocytes. Increased intracellular cAMP or inhibition of AMPK prevented both IL-1ß-induced NO release and mitochondrial dysfunction.


Assuntos
Condrócitos/efeitos dos fármacos , Inflamação/prevenção & controle , Interleucina-1beta/farmacologia , Mitocôndrias/efeitos dos fármacos , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Óxido Nítrico/metabolismo , Osteoartrite do Joelho/prevenção & controle , Células Cultivadas , Condrócitos/metabolismo , Condrócitos/patologia , Feminino , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Mitocôndrias/patologia , NF-kappa B/genética , NF-kappa B/metabolismo , Osteoartrite do Joelho/induzido quimicamente , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia
2.
Medicine (Baltimore) ; 100(14): e25384, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832126

RESUMO

BACKGROUND: Knee osteoarthritis (KOA) is a major public health issue because it causes pain and functional limitation in patients. Many studies have reported that moxibustion, a treatment in traditional Chinese medicine, is effective in treating KOA. The aim of this protocol is to develop a standard in advance for synthesize and assess the efficacy and safety of thunder-fire moxibustion for KOA from these randomized controlled trial. METHODS: The 2 commentators will screen 7 databases (PubMed, EMBASE, the Cochrane Library, Chinese National Knowledge Infrastructure, Chinese VIP Information, Wanfang Database, and Chinese Biomedical Literature Database) for randomized controlled trials that can be included from the time the database is built up until publication in December 2020. The original study that randomized control trials of thunder-fire moxibustion for patients with KOA will be selected and is not limited by country or language. In addition, researches in progress, the reference lists, and the citation lists of identified publications will be retrieved similarly. Study selection, data extraction, and assessment of the quality will be performed independently by 2 reviewers who have been trained before data extraction. A meta-analysis will be conduct if the quantity and quality of the original studies included are satisfactory; otherwise, a descriptive analysis will be conducted. Review Manager 5.4 software (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) will be using for data synthesis and assessment the risk of bias according to Cochrane Handbook. RESULT: This study will provide a comprehensive review of current evidence for the treatment of thunder-fire moxibustion on KOA. CONCLUSION: The conclusion of this study will provide a judging basis that whether the treatment of KOA with thunder-fire moxibustion is effective. REGISTRATION NUMBER: INPLASY2020100012.


Assuntos
Medicina Tradicional Chinesa/métodos , Moxibustão/métodos , Osteoartrite do Joelho/terapia , Manejo da Dor/métodos , Bases de Dados Factuais , Feminino , Humanos , Masculino , Moxibustão/efeitos adversos , Osteoartrite do Joelho/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
3.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33799588

RESUMO

We have been studying mesenchymal stem cells (MSCs) in synovial fluid and the intra-articular injection of synovial MSCs in osteoarthritis (OA) knees. Here, mainly based on our own findings, we overview the characteristics of endogenous MSCs in the synovial fluid of OA knees and their mode of action when injected exogenously into OA knees. Many MSCs similar to synovial MSCs were detected in the synovial fluid of human OA knees, and their number correlated with the radiological OA grade. Our suspended synovium culture model demonstrated the release of MSCs from the synovium through a medium into a non-contacting culture dish. In OA knees, endogenous MSCs possibly mobilize in a similar manner from the synovium through the synovial fluid and act protectively. However, the number of mobilized MSCs is limited; therefore, OA progresses in its natural course. Synovial MSC injections inhibited the progression of cartilage degeneration in a rat OA model. Injected synovial MSCs migrated into the synovium, maintained their MSC properties, and increased the gene expressions of TSG-6, PRG-4, and BMP-2. Exogenous synovial MSCs can promote anti-inflammation, lubrication, and cartilage matrix synthesis in OA knees. Based on our findings, we have initiated a human clinical study of synovial MSC injections in OA knees.


Assuntos
Condrogênese/genética , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/fisiologia , Osteoartrite do Joelho/terapia , Líquido Sinovial/fisiologia , Animais , Proteína Morfogenética Óssea 2/genética , Proteína Morfogenética Óssea 2/metabolismo , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Injeções Intra-Articulares , Células-Tronco Mesenquimais/citologia , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Proteoglicanas/genética , Proteoglicanas/metabolismo , Ratos , Líquido Sinovial/citologia , Transplante Heterólogo , Resultado do Tratamento
4.
Int J Mol Sci ; 22(5)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800401

RESUMO

Osteoarthritis (OA) is a progressive degenerative disease that manifests as pain and inflammation and often results in total joint replacement. There is significant interest in understanding how intra-articular injections made from autologous blood or bone marrow could alleviate symptoms and potentially intervene in the progression of the disease. There is in vitro an in vivo evidence that suggests that these therapies, including platelet-rich plasma (PRP), autologous anti-inflammatories (AAIs), and concentrated bone marrow aspirate (cBMA), can interrupt cartilage matrix degradation driven by pro-inflammatory cytokines. This review analyzes the evidence for and against inclusion of white blood cells, the potential role of platelets, and the less studied potential role of blood plasma when combining these components to create an autologous point-of-care therapy to treat OA. There has been significant focus on the differences between the various autologous therapies. However, evidence suggests that there may be more in common between groups and perhaps we should be thinking of these therapies on a spectrum of the same technology, each providing significant levels of anti-inflammatory cytokines that can be antagonists against the inflammatory cytokines driving OA symptoms and progression. While clinical data have demonstrated symptom alleviation, more studies will need to be conducted to determine whether these preclinical disease-modifying findings translate into clinical practice.


Assuntos
Anti-Inflamatórios/uso terapêutico , Osteoartrite do Joelho/terapia , Plasma Rico em Plaquetas , Sistemas Automatizados de Assistência Junto ao Leito , Humanos , Injeções Intra-Articulares , Articulação do Joelho/imunologia , Articulação do Joelho/patologia , Osteoartrite do Joelho/imunologia , Osteoartrite do Joelho/patologia
5.
Int J Mol Sci ; 22(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802838

RESUMO

Osteoarthritis (OA) is a multifactorial disease which is characterized by a change in the homeostasis of the extracellular matrix (ECM). The ECM is essential for the function of the articular cartilage and plays an important role in cartilage mechanotransduction. To provide a better understanding of the interaction between the ECM and the actin cytoskeleton, we investigated the localization and expression of the Ca2+-dependent proteins cartilage oligomeric matrix protein (COMP), thrombospondin-1 (TSP-1), plastin 3 (PLS3) and stromal interaction molecule 1 (STIM1). We investigated 16 patients who suffered from varus knee OA and performed a topographical analysis of the cartilage from the medial and lateral compartment of the proximal tibial plateau. In a varus knee, OA is more pronounced in the medial compared to the lateral compartment as a result of an overloading due to the malalignment. We detected a location-dependent staining of PLS3 and STIM1 in the articular cartilage tissue. The staining intensity for both proteins correlated with the degree of cartilage degeneration. The staining intensity of TSP-1 was clearly reduced in the cartilage of the more affected medial compartment, an observation that was confirmed in cartilage extracts by immunoblotting. The total amount of COMP was unchanged; however, slight changes were detected in the localization of the protein. Our results provide novel information on alterations in OA cartilage suggesting that Ca2+-dependent mechanotransduction between the ECM and the actin cytoskeleton might play an essential role in the pathomechanism of OA.


Assuntos
Cartilagem Articular/metabolismo , Articulação do Joelho/metabolismo , Glicoproteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Osteoartrite do Joelho/metabolismo , Molécula 1 de Interação Estromal/metabolismo , Trombospondinas/metabolismo , Idoso , Idoso de 80 Anos ou mais , Proteína de Matriz Oligomérica de Cartilagem/metabolismo , Condrócitos/metabolismo , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Transporte Proteico
6.
Life Sci ; 275: 119375, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33737085

RESUMO

AIMS: Both aerobic exercise and glucosamine hydrochloride capsules (OTL) have a therapeutic effect on knee osteoarthritis, but their joint application has not been investigated. This study clarified the mechanism of the combined treatment in knee osteoarthritis. MAIN METHODS: Aerobic exercise and OTL were used alone or in combination to treat papain-induced knee osteoarthritis model rabbits. Pathological changes of cartilage tissues, inflammatory cytokine content, glycosaminoglycan, and expressions of collagen II, cartilage differentiation-related genes and circUNK were analyzed by hematoxylin-eosin staining, Mankin score, Enzyme-linked immunosorbent assay, toluidine blue staining, Immunohistochemistry and qRT-PCR. The extracted chondrocytes were identified by Alcian Blue staining and immunohistochemistry and induced by iodoacetic acid (MIA) to establish osteoarthritis model. Effects of overexpressing or silencing circUNK on cell function and molecular changes in chondrocytes were analyzed by cell function experiments, qRT-PCR and Western blot. Rabbit modeling and intervention treatment were marked. KEY FINDINGS: Aerobic exercise or OTL treatment alone relieved the damage caused by knee osteoarthritis in terms of cartilage tissue lesions, Mankin score, inflammatory cytokine content, glycosaminoglycan, and expressions of collagen II, cartilage differentiation-related genes and circUNK. Combined application of aerobic exercise and OTL showed better synergistic treatment effects. Transfection of overexpressed circUNK could attenuate the MIA-induced effect on cell viability and apoptosis in chondrocytes by regulating genes related to differentiation and apoptosis. Aerobic exercise combined with glucosamine had a synergistic therapeutic effect on knee osteoarthritis. SIGNIFICANCE: Overexpressing circUNK protected osteoarthritis model cells by regulating cartilage differentiation- and apoptosis-related genes.


Assuntos
Glucosamina/uso terapêutico , Osteoartrite do Joelho/terapia , Condicionamento Físico Animal , RNA Circular/metabolismo , Animais , Western Blotting , Cartilagem Articular/patologia , Condrócitos/patologia , Terapia Combinada , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , Osteoartrite do Joelho/patologia , Condicionamento Físico Animal/métodos , Coelhos , Reação em Cadeia da Polimerase em Tempo Real
7.
Bone Joint J ; 103-B(2): 329-337, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517740

RESUMO

AIMS: A comprehensive classification for coronal lower limb alignment with predictive capabilities for knee balance would be beneficial in total knee arthroplasty (TKA). This paper describes the Coronal Plane Alignment of the Knee (CPAK) classification and examines its utility in preoperative soft tissue balance prediction, comparing kinematic alignment (KA) to mechanical alignment (MA). METHODS: A radiological analysis of 500 healthy and 500 osteoarthritic (OA) knees was used to assess the applicability of the CPAK classification. CPAK comprises nine phenotypes based on the arithmetic HKA (aHKA) that estimates constitutional limb alignment and joint line obliquity (JLO). Intraoperative balance was compared within each phenotype in a cohort of 138 computer-assisted TKAs randomized to KA or MA. Primary outcomes included descriptive analyses of healthy and OA groups per CPAK type, and comparison of balance at 10° of flexion within each type. Secondary outcomes assessed balance at 45° and 90° and bone recuts required to achieve final knee balance within each CPAK type. RESULTS: There was similar frequency distribution between healthy and arthritic groups across all CPAK types. The most common categories were Type II (39.2% healthy vs 32.2% OA), Type I (26.4% healthy vs 19.4% OA) and Type V (15.4% healthy vs 14.6% OA). CPAK Types VII, VIII, and IX were rare in both populations. Across all CPAK types, a greater proportion of KA TKAs achieved optimal balance compared to MA. This effect was largest, and statistically significant, in CPAK Types I (100% KA vs 15% MA; p < 0.001), Type II (78% KA vs 46% MA; p = 0.018). and Type IV (89% KA vs 0% MA; p < 0.001). CONCLUSION: CPAK is a pragmatic, comprehensive classification for coronal knee alignment, based on constitutional alignment and JLO, that can be used in healthy and arthritic knees. CPAK identifies which knee phenotypes may benefit most from KA when optimization of soft tissue balance is prioritized. Further, it will allow for consistency of reporting in future studies. Cite this article: Bone Joint J 2021;103-B(2):329-337.


Assuntos
Artroplastia do Joelho , Mau Alinhamento Ósseo/classificação , Articulação do Joelho/patologia , Osteoartrite do Joelho/cirurgia , Assistência Perioperatória/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/métodos , Fenômenos Biomecânicos , Mau Alinhamento Ósseo/complicações , Mau Alinhamento Ósseo/diagnóstico , Mau Alinhamento Ósseo/fisiopatologia , Estudos de Casos e Controles , Feminino , Humanos , Articulação do Joelho/fisiopatologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/fisiopatologia , Equilíbrio Postural , Estudos Prospectivos , Resultado do Tratamento
8.
Life Sci ; 268: 118992, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33417956

RESUMO

Osteoarthritis (OA) is a common chronic degenerative disease that affects the elderly. Thus far, no pharmacological therapy approved by regulators has shown a convincing effect on OA. Glabridin, a small molecule, is a well-known and powerful natural antioxidant, which has a strong scavenging effect on free radicals. This study attempted to explore the role and underlying mechanisms of Glabridin on OA both in vitro and in vivo. In the in vitro study, Glabridin was found to increase the expression levels of extracellular matrix (ECM) related genes, Collagen II, Aggrecan (ACAN), SRY-box 9 (SOX9) and proteoglycan 4 (PRG4). Moreover, Glabridin was observed to significantly reduce the level of oxidative stress in OA chondrocytes while effectively reducing the apoptosis of chondrocytes. Glabridin was also found to significantly increase the autophagy of human OA chondrocytes. During the in vivo study, intraarticular injection of Glabridin was observed to alleviate OA progression and protect chondrocytes against apoptosis following anterior cruciate ligament transection (ACLT) in rats. Furthermore, the mammalian target of rapamycin (mTOR) mediated autophagy was identified as one of the potential mediators of Glabridin activity. Overall, Glabridin protects articular cartilage from damage in rats with OA by protecting chondrocytes against oxidative stress, apoptosis and promoting mTOR mediated autophagy.


Assuntos
Condrócitos/efeitos dos fármacos , Isoflavonas/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Animais , Ligamento Cruzado Anterior/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Cartilagem Articular/patologia , Catalase/metabolismo , Condrócitos/metabolismo , Condrócitos/patologia , Proteínas da Matriz Extracelular/genética , Humanos , Injeções Intra-Articulares , Isoflavonas/administração & dosagem , Masculino , Osteoartrite do Joelho/etiologia , Osteoartrite do Joelho/metabolismo , Osteoartrite do Joelho/patologia , Estresse Oxidativo/fisiologia , Fenóis/administração & dosagem , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Serina-Treonina Quinases TOR/metabolismo
9.
Int J Mol Sci ; 22(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33430025

RESUMO

As the leading cause of disability, osteoarthritis (OA) affects people of all ages, sexes, and races. With the increasing understanding of OA, the sex differences have attracted specific attention as the burden of OA is greater in women. There is no doubt that gender-specific OA management has great potential for precision treatment. On the other hand, from the marketing aspect, a medication targeting the OA-responsive biomarker(s) shared by both genders is more favorable for drug development. Thus, in the current study, a published transcriptome dataset of knee articular cartilage was used to compare OA and healthy samples for identifying the genes with the same significantly different expression trend in both males and females. With 128 genes upregulated and 143 genes downregulated in both OA males and females, 9 KEGG pathways have been enriched based on the current knowledge, including 'renal cell carcinoma,' 'ECM-receptor interaction,' 'HIF-1 signaling pathway,' 'MicroRNAs in cancer,' 'focal adhesion,' 'Relaxin signaling pathway,' 'breast cancer,' 'PI3K-Akt signaling pathway,' and 'human papillomavirus infection.' Here, we explore the potential impacts of these clusters in OA. We also analyze the identified 'cell plasma membrane related genes' in-depth to identify the potential chondrocyte cell surface target(s) of OA management.


Assuntos
Cartilagem/metabolismo , MicroRNAs/genética , Osteoartrite do Joelho/genética , Transcriptoma/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Cartilagem/crescimento & desenvolvimento , Condrócitos/metabolismo , Feminino , Regulação da Expressão Gênica/genética , Humanos , Articulação do Joelho/metabolismo , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/patologia , Caracteres Sexuais , Transdução de Sinais/genética
10.
Life Sci ; 267: 118893, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33316267

RESUMO

OBJECTIVE: In recent decades, the role of microRNAs (miRNAs) in human diseases has been widely studied. This research is designed to explore the effect of miR-218-5p on knee osteoarthritis (KOA) progression in a rat model with the involvement of sclerostin (SOST). METHODS: The KOA rat models were constructed by Hulth method, and then were classified into the KOA, miR-218-5p inhibitor, inhibitor negative control (NC), overexpressed (OE)-SOST, OE-NC, miR-218-5p inhibitor + si-SOST, or miR-218-5p inhibitor + si-NC group. The pathological changes of rats' synovial tissues were observed; the apoptosis in rat synovial tissues was assessed; levels of IL-1ß, TNF-α, PGE2 and COX-2 in serum and synovial tissues, along with SOD and MDA contents in synovial tissues were determined. The morphological changes in cartilage tissues were observed. MMP-13 and Col II expression in cartilage tissues was assessed; expression of ß-catenin and Col2A1 in cartilage tissues was assessed. miR-218-5p and SOST expression in rat knee joint tissues was assessed. RESULTS: KOA rats had increased miR-218-5p expression and decreased SOST expression. MiR-218-5p targeted SOST. Rats injected with miR-218-5p inhibitor and OE-SOST had alleviated pathological changes, reduced TUNEL positive cell rate, decreased serum contents of IL-1ß, TNF-α, PGE2, COX-2 and MDA, and increased SOD activity in synovial tissues, alleviated pathological changes, enhanced Col II positive rate and reduced MMP-13 positive rate, decreased ß-catenin expression and increased Col2A1 expression in cartilage tissues. CONCLUSION: The miR-218-5p inhibition could attenuate synovial inflammation and cartilage injury in KOA rats by promoting SOST, which may be helpful for KOA treatment.


Assuntos
Proteínas Morfogenéticas Ósseas/metabolismo , Cápsula Articular/patologia , MicroRNAs/antagonistas & inibidores , Osteoartrite do Joelho/metabolismo , Animais , Apoptose/fisiologia , Proteínas Morfogenéticas Ósseas/genética , Cartilagem/metabolismo , Cartilagem/patologia , Ciclo-Oxigenase 2/metabolismo , Marcadores Genéticos/genética , Membro Posterior/patologia , Cápsula Articular/metabolismo , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Membrana Sinovial/metabolismo , Membrana Sinovial/patologia
11.
Methods Mol Biol ; 2221: 223-260, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32979207

RESUMO

The surgical model of destabilization of the medial meniscus (DMM) has become a gold standard for studying the onset and progression of post-traumatic osteoarthritis (OA). The DMM model mimics clinical meniscal injury, a known predisposing factor for the development of human OA, and permits the study of structural and biological changes over the course of the disease. In addition, when applied to genetically modified or engineered mouse models, this surgical procedure permits dissection of the relative contribution of a given gene to OA initiation and/or progression. This chapter describes the requirements for the surgical induction of OA in mouse models, and provides guidelines and tools for the subsequent histological, immunohistochemical, and molecular analyses. Methods for the assessment of the contributions of selected genes in genetically modified strains are also provided.


Assuntos
Modelos Animais de Doenças , Meniscos Tibiais/patologia , Modelos Anatômicos , Osteoartrite do Joelho , Lesões do Menisco Tibial , Animais , Progressão da Doença , Masculino , Camundongos , Camundongos Transgênicos , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Lesões do Menisco Tibial/genética , Lesões do Menisco Tibial/cirurgia
12.
Mol Med Rep ; 23(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33300062

RESUMO

High mobility group box 1 (HMGB1) is an important downstream product of pyroptosis in macrophages, and it serves a vital role in numerous inflammatory diseases. Previous studies have reported that HMGB1 is released by fibroblast­like synoviocytes (FLSs) that are activated by inflammatory cytokines in knee osteoarthritis (KOA); however, the mechanism via which FLS promotes HMGB1 secretion in KOA remains unknown. According to our previous study, pyroptosis occurs in FLSs of patients with KOA and is mediated by Nod­like receptor protein (NLRP)1 or NLRP3 inflammasomes. However, the specific relationship between HMGB1 secretion and FLS pyroptosis requires further investigation. In the present study, the association between HMGB1 secretion and FLS pyroptosis was investigated in vitro and in vivo. In this study, western blotting, ELISA and reverse transcription­quantitative PCR were used to measure expression levels of proteins and mRNA. Caspase­1 activity assay and Hoechst 33342/PI double staining were used to observe the pyroptosis of FLSs. Hematoxylin and eosin staining was used to observe the destruction of cartilage in KOA. Increased expression levels of pyroptosis­related proteins and HMGB1 in the synovium of rat anterior cruciate ligament transection­induced KOA models were identified, and these changes were significantly mitigated via the intra­articular injection of a caspase­1 inhibitor. In vitro, FLSs were treated with lipopolysaccharide (LPS) + ATP to induce pyroptosis, and HMGB1 secretion was subsequently measured. LPS + ATP significantly increased the expression levels of pyroptosis­related proteins and HMGB1 in FLSs, and these effects were significantly mitigated by small interfering RNAs targeting NLRP1, NLRP3, apoptosis­associated speck­like protein with a caspase­recruitment domain or caspase­1. Therefore, the present results indicated that NLRP1/NLRP3 inflammasome­mediated and caspase­1­dependent FLS pyroptosis increased HMGB1 secretion in KOA. These findings may provide a therapeutic strategy to decrease synovial inflammatory responses during KOA progression.


Assuntos
Fibroblastos/metabolismo , Proteína HMGB1/metabolismo , Osteoartrite do Joelho/metabolismo , Piroptose , Sinoviócitos/metabolismo , Animais , Modelos Animais de Doenças , Fibroblastos/patologia , Masculino , Osteoartrite do Joelho/patologia , Ratos , Ratos Sprague-Dawley , Sinoviócitos/patologia
13.
Medicine (Baltimore) ; 99(40): e22538, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019462

RESUMO

The current studies revealed inconsistent relationship between reproductive factors and osteoarthritis. Community-based research has not been conducted in China. The study was to examine the association of reproductive factors with the prevalence of knee osteoarthritis (OA).Through a multistage stratified random sampling method, 10 streets or villages from 5 cities in Hunan province were randomly selected, a total 2746 eligible women aged 50 to 83 were recruited in this cross-sectional study. A structured questionnaire including demographic factors, socio-economic status, reproductive factors, and knee OA was used. According to the criteria of American College of Rheumatology, clinical knee OA was assessed by doctors in community or village health clinics for knee pain, age, morning stiffness, crepitus on active motion or for knee pain, morning stiffness, crepitus on active motion, and tenderness of the bony navigation of the joint. Self-reported age of menarche, parity, abortion history, and menopausal status were collected.The prevalence of knee OA was 13.44%. Abortion is associated with knee OA (odds ratio [OR] = 1.271, 95% confidence interval [CI] = 1.007, 1.606), but age at menarche, parity, and menopausal status were not the factors. Furthermore, age (OR = 1.040, 95% CI = 1.020, 1.060), weight (OR = 1.019, 95% CI = 1.004, 1.035), higher education level (OR = 1.530, 95% CI = 1.121, 2.088), higher monthly household income (OR = .583, 95% CI = 0.441, 0.770 for 3000-4999 ¥ and OR = 0.599, 95% CI = 0.431, 0.833 for 5000 ¥ or more), and chronic gastritis (OR = 3.364, 95% CI = 2.548, 4.442) were associated with knee OA.Abortion may increase the risk of knee OA. Special attention should be paid to women with a history of abortion, and women who are planning to abort should be informed of the risk of knee OA later in life. The relationship between abortion and knee OA should be interpreted with caution and further confirmed.


Assuntos
Aborto Espontâneo/epidemiologia , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/etiologia , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Dor/diagnóstico , Dor/epidemiologia , Prevalência , Radiografia/métodos , Medição de Risco , Autorrelato , Classe Social , Inquéritos e Questionários
14.
PLoS One ; 15(9): e0238024, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32991606

RESUMO

INTRODUCTION: At present, information about clinical efficacy and adverse events of controlled release (CR) form of pelubiprofen, a prodrug of 2-arylopropionic acid with relatively selective effects on cyclooxygenase-2 activity, remains scarce. In this study, we sought to determine non-inferiority of pelubiprofen CR 90 mg/day compared to aceclofenac 200 mg/day regarding clinical efficacy and adverse events after a 4-week course of medication in the patients with symptomatic knee osteoarthritis. MATERIALS AND METHODS: A total of 191 patients were randomly assigned to take either pelubiprofen CR 90 mg (n = 95) or aceclofenac 200 mg (n = 96). The primary outcome variable was non-inferiority of pain reduction between baseline and week 4 when assessed using a 100 mm pain visual analogue scale (VAS). Pelubiprofen was considered non-inferior to aceclofenac if the upper limit of the one-sided 97.5% confidence interval for the difference in terms of pain VAS was above 15 mm (the average change of pain VAS in the pelubiprofen group-pain VAS reduction in the aceclofenac group). Secondary outcome variables were the changes in 100 mm pain VAS at week 2 versus baseline, K-Western Ontario, and McMaster University Arthritis Index (K-WOMAC) changes at weeks 2 and 4 as compared to baseline, patient global assessment at weeks 2 and 4. The frequency and amount of rescue medicine usage at weeks 2 and 4 were also evaluated as the secondary outcome variable. For safety analysis, adverse events, clinical laboratory tests, vital signs, and physical examinations were assessed and conducted at each follow-up visit. RESULTS: At week 4, the pain VAS values were significantly reduced in both groups receiving either pelubiprofen CR 90 mg or aceclofenac 200 mg as compared to the baseline. However, the pelubiprofen group and the aceclofenac group respectively showed the pain VAS changes of -22 and -21.9 in the pre-protocol set and -20.8 and -21.7 in the full analysis set, confirming non-inferiority. The pelubiprofen CR 90 mg showed a reduced incidence of adverse events compared to the aceclofenac 200 mg (p = 0.005). CONCLUSIONS: Pelubiprofen CR 90 mg is as effective as aceclofenac 200 mg with reduced adverse events for the treatment of symptomatic knee osteoarthritis.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Diclofenaco/análogos & derivados , Osteoartrite do Joelho/tratamento farmacológico , Fenilpropionatos/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Diclofenaco/uso terapêutico , Método Duplo-Cego , Estudos de Equivalência como Asunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Medição da Dor , Segurança do Paciente , Resultado do Tratamento
15.
PLoS One ; 15(7): e0236865, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32730319

RESUMO

BACKGROUND: There is currently no standardized method for measuring functional status in knee osteoarthritis (OA) patients, despite that it is one of the top priorities when determining eligibility for total knee arthroplasty (TKA). The purpose of the current investigation was to identify factors associated with discordance between individual self-report and performance-based measures of function for obese and non-obese men and women with knee OA. METHODS: In a cohort of 727 knee OA patients scheduled for TKA, physical function prior to surgery was assessed with the self-reported physical function subscale of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC-pf), and the performance-based Timed Up and Go (TUG). Data on sociodemographic characteristics, health status, knee pain intensity, symptomatic joint site count, and pain catastrophizing were collected via questionnaire. The primary outcome was the difference in rescaled score between a participant's self-report and performance-based measures of function. Multivariable linear regression stratified by sex and obesity status was used to identify factors associated with discordance. RESULTS: The mean age of participants was 65.5 years and 55% were women. With younger age, self-reported scores indicated increasingly worse function compared to performance-based scores, regardless of sex or obesity status. Among non-obese individuals, greater knee pain intensity was associated with a participant's self-report score indicating increasingly worse function compared to their performance-based score. For obese women, pain catastrophizing, and number of symptomatic joints were also associated with discordance as was reporting fewer comorbidities. CONCLUSIONS: Physical function may be differentially represented by self-reported and performance-based measures depending on a variety of patient factors. Our findings add to the evidence which suggests both measures should be used when assessing functional status prior to TKA.


Assuntos
Obesidade/fisiopatologia , Osteoartrite do Joelho/psicologia , Osteoartrite do Joelho/cirurgia , Avaliação de Resultados em Cuidados de Saúde/métodos , Desempenho Físico Funcional , Qualidade de Vida , Autorrelato , Atividades Cotidianas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Medição da Dor , Prognóstico , Estudos Prospectivos , Recuperação de Função Fisiológica , Índice de Gravidade de Doença , Fatores Sexuais , Inquéritos e Questionários
16.
Medicine (Baltimore) ; 99(28): e20907, 2020 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-32664084

RESUMO

BACKGROUND: The increasing prevalence of osteoarthritis among the old population worldwide is a great concern. Two of the biggest complaints of OA patients are joint pain and inflammation. Currently, people are relying on non-steroidal anti-inflammatory drugs (NSAIDs) and steroids to control pain and inflammation. However, long-term use of these pharmaceutical drugs has negative health consequences in the elderly, including gastro-intestinal, respiratory, and renal diseases. Natural products are receiving more attention than ever as alternative treatments against OA for their efficacies and safety. The root of Paeonia lactiflora Pal and the gum resin of Commiphora myrrha have been used as analgesics and anti-inflammatory agents since ancient time. A new herbal formula composed of P. lactiflora root and C. myrrha gum resin extracts, known as HT083, has shown promising antinociceptive and anti-inflammatory effects in a rodent model of OA. We design this study to investigate the safety and the efficacy of HT083 to prevent OA in patients with mild OA. METHODS: This is a randomized, double-blind, and placebo-controlled study. A total of 100 eligible participants will be divided into two groups and will be given HT083 and a placebo for 12 weeks in 1:1 ratio. Treatment results will be assessed using a visual analog scale (VAS), Korean-Short Form health survey-36 score (SF-36), personal evaluation, and laboratory analysis. DISCUSSION: This trial is expected to provide clinical evidence on the effectiveness and the safety of HT083 as a natural treatment for mild OA. TRIAL REGISTRATION: Korean Clinical Research Information Service (CRIS) number KCT0004925 Registered on 2020.04.16.


Assuntos
Artralgia/tratamento farmacológico , Indóis/uso terapêutico , Inflamação/tratamento farmacológico , Medicina Tradicional Chinesa/métodos , Osteoartrite do Joelho/tratamento farmacológico , Pirróis/uso terapêutico , Adulto , Idoso , Analgésicos/uso terapêutico , Animais , Anti-Inflamatórios/uso terapêutico , Commiphora/efeitos adversos , Commiphora/química , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/epidemiologia , Osteoartrite do Joelho/patologia , Paeonia/efeitos adversos , Paeonia/química , Placebos/administração & dosagem , República da Coreia/epidemiologia , Roedores , Segurança , Resultado do Tratamento , Escala Visual Analógica
17.
Sci Rep ; 10(1): 8852, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32483280

RESUMO

The cholinergic system plays a major anti-inflammatory role in many diseases through acetylcholine (Ach) release after vagus nerve stimulation. Osteoarthritis (OA) is associated with local low-grade inflammation, but the regulatory mechanisms are unclear. Local Ach release could have anti-inflammatory activity since articular cells express Ach receptors involved in inflammatory responses. Using the 3DISCO clearing protocol that allows whole-sample 3-dimensional (3D) analysis, we cleared human OA cartilage-subchondral bone samples to search for cholinergic nerve fibres able to produce Ach locally. We analysed 3 plugs of knee cartilage and subchondral bone from 3 OA patients undergoing arthroplasty. We found no nerves in the superficial and intermediate articular cartilage layers, as evidenced by the lack of Peripherin staining (a peripheral nerves marker). Conversely, peripheral nerves were found in the deepest layer of cartilage and in subchondral bone. Some nerves in the subchondral bone samples were cholinergic because they coexpressed peripherin and choline acetyltransferase (ChAT), a specific marker of cholinergic nerves. However, no cholinergic nerves were found in the cartilage layers. It is therefore feasible to clear human bone to perform 3D immunofluorescence. Human OA subchondral bone is innervated by cholinergic fibres, which may regulate local inflammation through local Ach release.


Assuntos
Imageamento Tridimensional/métodos , Articulação do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/patologia , Nervos Periféricos/patologia , Artroplastia do Joelho , Cartilagem Articular/diagnóstico por imagem , Fibras Colinérgicas/patologia , Humanos , Microscopia de Fluorescência , Osteoartrite do Joelho/terapia
18.
Ann Rheum Dis ; 79(8): 1105-1110, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32381567

RESUMO

OBJECTIVES: Although treatment development in osteoarthritis (OA) focuses on chondroprotection, it is unclear how much preventing cartilage loss reduces joint pain. It is also unclear how nociceptive tissues may be involved. METHODS: Using data from the Osteoarthritis Initiative, we quantified the relation between cartilage loss and worsening knee pain after adjusting for bone marrow lesions (BMLs) and synovitis, and examined how much these factors mediated this association. 600 knee MRIs were scored at baseline, 12 months and 24 months for quantitative and semiquantitative measures of OA structural features. We focused on change in medial cartilage thickness using an amount similar to that seen in recent trials. Linear models calculated mean change in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score with cartilage loss, adjusted for baseline BMLs, synovitis and covariates. Mediation analysis tested whether change in synovitis or BMLs mediated the cartilage loss-pain association. We carried out a subanalysis for knees with non-zero baseline WOMAC pain scores and another for non-valgus knees. RESULTS: Cartilage thickness loss was significantly associated with a small degree of worsening in pain over 24 months. For example, a loss of 0.1 mm of cartilage thickness over 2 years was associated with a 0.32 increase in WOMAC pain (scale 0-20). The association of cartilage thickness loss with pain was mediated by synovitis change but not by BML change. Subanalysis results were similar. CONCLUSIONS: Cartilage thickness loss is associated with only a small amount of worsening knee pain, an association mediated in part by worsening synovitis. Demonstrating that chondroprotection reduces knee pain will be extremely challenging and is perhaps unachievable.


Assuntos
Artralgia/etiologia , Cartilagem Articular/patologia , Osteoartrite do Joelho/patologia , Idoso , Feminino , Humanos , Articulação do Joelho/patologia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/complicações
19.
AJR Am J Roentgenol ; 215(2): 441-447, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32374669

RESUMO

OBJECTIVE. Cartilage loss on preoperative knee MRI is a predictor of poor outcomes after arthroscopic partial meniscectomy. The purpose of this study was to compare the ability to predict outcomes after arthroscopic partial meniscectomy with a clinically used modified Outerbridge system versus a semiquantitative MRI Osteoarthritis Knee Score system for grading cartilage loss. MATERIALS AND METHODS. Patients who underwent preoperative knee MRI within 6 months of arthroscopic partial meniscectomy and who had outcomes available from the time of surgery and 1 year later were eligible for inclusion. Cases were evaluated by two radiologists and one radiology fellow with the use of both grading systems. The accuracy of each system in discriminating between surgical success and failure was estimated using the ROC curve (AUC) with 95% CIs. A Wald test was used to assess noninferiority of the clinical grading system. Interreader agreement regarding the accuracy of the grading systems in predicting outcomes was also compared. RESULTS. A total of 78 patients (38 women and 40 men; mean age, 56.6 years) were included in the study. A prediction model using clinical grading (AUC = 0.695; 95% CI, 0.566-0.824) was noninferior (p = 0.047) to a model using MRI Osteoarthritis Knee Score grading (AUC = 0.683; 95% CI, 0.539-0.827). Both MRI prediction models performed better than a model using demographic characteristics only (AUC = 0.667; 95% CI, 0.522-0.812). Inter-reader agreement with clinical grading (80.8%) was higher than that with MRI Osteoarthritis Knee Score grading (65.0%; p = 0.012). CONCLUSION. A clinically used system to grade cartilage loss on MRI is as effective as a semiquantitative system for predicting outcomes after arthroscopic partial meniscectomy, while also offering improved interreader agreement.


Assuntos
Artroscopia , Cartilagem Articular/diagnóstico por imagem , Cartilagem Articular/patologia , Imagem por Ressonância Magnética , Meniscectomia/métodos , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Resultado do Tratamento
20.
Libyan J Med ; 15(1): 1753943, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32281500

RESUMO

Knee Osteoarthritis is a considerable public health concern, both in terms of life quality and treatment financial impacts. To investigate this disease, animal models are deemed a promising alternative. In fact, although a perfect model is generally farfetched, the creation of models that simulate human disease as accurately as possible remains an important research stake. This study aims to highlight the usefulness of the model induced by injected Mono-Iodo-Acetate and to standardize it for the rabbit species. Osteoarthritis was induced by an infra-patellar injection of 0.2 ml of an MIA solution in the left knee of 24 female New Zealand rabbits. The right knee served as a control by receiving an injection of physiological serum. The rabbits were divided into 4 groups of 6 individuals each according to the dose of MIA received per knee. All rabbits were euthanized 30 days after the injection. After sacrifice, the knees were carefully dissected and macroscopic and microscopic scores of cartilage, meniscal and synovial lesions were attributed to each group. Our study followed the laboratory animal care and management guideline published in 2017 by the Canadian Council of Animal Care. The control knees of all rabbits showed no macroscopic or microscopic lesions. The macroscopic lesions: osteophytes, meniscal lesions, fibrillation and erosion of the cartilage and microscopic lesions: disorganization of the chondrocytes, decrease in proteoglycans and synovial inflammation clinically diagnosed in human pathology were all detected and were similarly reproducible among the knees of the same group. Through this work, we highlighted the merits of the arthritis model induced by MIA, namely its simulation of several aspects of human pathology. Further advantages are low cost, speed, reproducibility. This model notably avoids delicate and risky surgical operations.


Assuntos
Inibidores Enzimáticos/administração & dosagem , Ácido Iodoacético/administração & dosagem , Osteoartrite do Joelho/induzido quimicamente , Animais , Bolsa Sinovial/patologia , Bolsa Sinovial/ultraestrutura , Canadá/epidemiologia , Cartilagem/patologia , Cartilagem/ultraestrutura , Condrócitos/patologia , Modelos Animais de Doenças , Inibidores Enzimáticos/efeitos adversos , Feminino , Humanos , Injeções/métodos , Ácido Iodoacético/efeitos adversos , Menisco/patologia , Menisco/ultraestrutura , Osteoartrite do Joelho/patologia , Osteoartrite do Joelho/veterinária , Proteoglicanas/metabolismo , Coelhos , Reprodutibilidade dos Testes
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