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1.
Life Sci ; 240: 116857, 2020 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-31521691

RESUMEN

AIMS: Daphnetin (DAP) is a traditional Chinese drug usually used to treat cardiovascular diseases. Studies have confirmed the anti-inflammatory, antioxidant, anti-bacterial and insecticidal, anti-tumor and neuro-protective effects of DAP. However, its anti-arthritic potential remains unexplored. The aim of this study is to investigate the in vitro and in vivo chondroprotective effects of DAP. MAIN METHODS: The effect of DAP on primary rabbit chondrocytes was examined using recombinant human IL-1ß for 24 h. For the in vivo studies, rabbits were randomly divided into groups: a normal control group and osteoarthritis (OA) groups. The OA groups received three different doses of DAP for 4 or 8 weeks. The anti-arthritic effect of DAP was assessed using histopathological examinations, qRT-PCR, western blotting and immunohistochemical analysis. KEY FINDINGS: Both in vitro and in vivo results indicate that DAP exerts a protective effect against IL-1ß in chondrocytes. In vitro, DAP inhibits the expression of IL-6, IL-12, MMP-3, MMP-9 and MMP-13, induced by IL-1ß in rabbit chondrocytes, and stimulates the production of IL-10. The inhibitory effect of DAP on the MMPs is partially regulated by the inhibition of the PI3K/AKT, MAPK and NF-κB signaling pathways. The effect of DAP on OA may be attributed to the suppression of inflammatory factor secretion, chondrocyte apoptosis observed by the decrease in pro-apoptotic Caspase-3 and BAX, and the activation of anti-apoptotic BCL-2. SIGNIFICANCE: DAP has a broad range of prospects in the treatment of OA, which provides a novel therapeutic strategy for OA.


Asunto(s)
Antirreumáticos/uso terapéutico , Condrocitos/efectos de los fármacos , Osteoartritis/tratamiento farmacológico , Sustancias Protectoras/uso terapéutico , Umbeliferonas/uso terapéutico , Animales , Antirreumáticos/efectos adversos , Apoptosis/efectos de los fármacos , Cartílago Articular/efectos de los fármacos , Cartílago Articular/patología , Supervivencia Celular , Condrocitos/patología , Citocinas/antagonistas & inhibidores , Citocinas/biosíntesis , Relación Dosis-Respuesta a Droga , Interleucina-1beta/farmacología , Masculino , Osteoartritis/patología , Cultivo Primario de Células , Conejos , Transducción de Señal/efectos de los fármacos , Umbeliferonas/efectos adversos
2.
Toxicol Lett ; 321: 122-130, 2020 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-31874197

RESUMEN

Our previous studies confirmed that prenatal caffeine exposure (PCE) could induce susceptibility to osteoarthritis in adult offspring rats due to poor chondrocyte differentiation, but its mechanism remains to be further investigated. This study aimed to explore whether subchondral bone dysplasia mediates susceptibility to osteoarthritis in adult offspring rats induced by PCE. Pregnant Wistar rats were treated with caffeine (120 mg/kg.d) or saline from gestational day (GD) 9 to 20. The female offspring were euthanized to collect femurs at GD20, postnatal week (PW) 6, and PW28 (non-ovariectomy and ovariectomy groups) to detect osteoarthritis-like phenotype, subchondral bone mass, ossification center development, and other evidence. The results showed that PCE increased the Mankin score of pathological articular cartilage, but decreased articular cartilage thickness and subchondral bone mass, which were more obvious after ovariectomy. Meanwhile, the correlation analysis results demonstrated that the Mankin score of articular cartilage was significantly negatively correlated with subchondral bone mass, and the thickness of articular cartilage was significantly positively correlated with subchondral bone mass. Further, the length and area of the primary and secondary ossification centers, the number of osteoblasts, and the related genes' expression of osteogenic differentiation (e.g., Runx2, BSP, ALP, and OCN) were all significantly decreased in the PCE group before and after birth. Taken together, PCE induced susceptibility to osteoarthritis in adult female offspring, which was likely related to the subchondral bone dysplasia and reduction of subchondral bone mass production due to developmental disorder of primary and secondary ossification centers caused by osteoblast differentiation disability before and after birth.


Asunto(s)
Enfermedades del Desarrollo Óseo/inducido químicamente , Cafeína/toxicidad , Cartílago Articular/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/toxicidad , Osteoartritis/inducido químicamente , Osteogénesis/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal , Factores de Edad , Animales , Enfermedades del Desarrollo Óseo/genética , Enfermedades del Desarrollo Óseo/metabolismo , Enfermedades del Desarrollo Óseo/patología , Cartílago Articular/patología , Diferenciación Celular/efectos de los fármacos , Femenino , Fémur/efectos de los fármacos , Fémur/metabolismo , Fémur/patología , Edad Gestacional , Osteoartritis/genética , Osteoartritis/metabolismo , Osteoartritis/patología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteoblastos/patología , Osteogénesis/genética , Ovariectomía , Embarazo , Ratas Wistar , Factores Sexuales , Tibia/efectos de los fármacos , Tibia/metabolismo , Tibia/patología
3.
Biomed Khim ; 65(6): 441-456, 2019 Oct.
Artículo en Ruso | MEDLINE | ID: mdl-31876515

RESUMEN

Osteoarthritis and type 2 diabetes mellitus represent two the most common chronic diseases. They possess many shared epidemiologic traits, have common risk factors, and embody heterogeneous multifactorial pathologies, which develop due to interaction of genetic an environmental factors. In addition, these diseases are often occurring in the same patient. In spite of the differences in clinical manifestation both diseases have similar disturbances of cellular metabolism, primarily associated with ATP production and utilization. The review discusses molecular mechanisms determining pathophysiological processes associated with glucose and lipid metabolism as well as the means aiming to alleviate the disturbances of energy metabolism as a new a therapeutic approach.


Asunto(s)
Diabetes Mellitus Tipo 2/patología , Metabolismo Energético , Glucosa/metabolismo , Metabolismo de los Lípidos , Osteoartritis/patología , Dolor , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Osteoartritis/metabolismo
4.
Yonsei Med J ; 60(11): 1081-1092, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31637891

RESUMEN

PURPOSE: Accumulating evidence suggests that microRNA-145 (miR-145) plays an important role in osteoarthritis (OA), which is a chronic progressive joint disease. Long noncoding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) promotes metastasis in cancers and functions as a sponge for miR-145. However, the role of MALAT1/miR-145 in OA pathogenesis has not yet been elucidated. MATERIALS AND METHODS: The expression of MALAT1 and miR-145 was examined by quantitative real-time PCR; the interaction between miR-145, MALAT1 and a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) 5 was verified by luciferase reporter assay. Correlations among MALAT1, miR-145, and ADAMTS5 were analyzed by Spearman rank analysis. Chondrocytes viability and cartilage extracellular matrix (ECM) degradation were investigated with cell viability assay and Western blotting analyzing expression of ADAMTS5, collagen type 2 alpha 1 (COL2A1), aggrecan (ACAN), and cartilage oligomeric matrix protein (COMP). RESULTS: MALAT1 was upregulated, and miR-145 was downregulated in OA samples and IL-1ß-induced chondrocytes. Mechanically, miR-145 could directly bind to MALAT1 and ADAMTS5. Moreover, miR-145 expression was negatively correlated with MALAT1 and ADAMTS5 expression in OA patients, whereas MALAT1 and ADAMTS5 expression was positively correlated. Functionally, overexpression of MALAT1 inhibited chondrocyte viability and promoted cartilage ECM degradation in IL-1ß-induced chondrocytes. In support thereof, MALAT1 silencing and miR-145 upregulation exerted the opposite effect in IL-1ß-induced chondrocytes. Moreover, the effect of MALAT1 was counteracted by miR-145 upregulation, and ADAMTS5 restoration could abate miR-145 effects. CONCLUSION: An MALAT1/miR-145 axis contributes to ECM degradation in IL-1ß-induced chondrocytes through targeting ADAMTS5, suggesting that MALAT1/miR-145/ADAMTS5 signaling may underlie human OA pathogenesis.


Asunto(s)
Proteína ADAMTS5/genética , Cartílago Articular/patología , Condrocitos/patología , Matriz Extracelular/metabolismo , Interleucina-1beta/efectos adversos , MicroARNs/metabolismo , Osteoartritis/genética , ARN Largo no Codificante/metabolismo , Proteína ADAMTS5/metabolismo , Adulto , Anciano , Secuencia de Bases , Supervivencia Celular/genética , Células Cultivadas , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Masculino , MicroARNs/genética , Osteoartritis/patología , ARN Largo no Codificante/genética
5.
Clin Exp Rheumatol ; 37 Suppl 120(5): 57-63, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31621560

RESUMEN

Although osteoarthritis (OA) was historically referred to as the non-inflammatory arthritis, it is now considered a condition involving persistent low-grade inflammation and activation of innate inflammatory pathways. Synovitis increases the risk of OA onset and progression and involves the recruitment of monocytes, lymphocytes, and other leukocytes. In particular, macrophages are important mediators of synovial inflammatory activity and pathologic cartilage and bone responses that are characteristic of OA. Advances in understanding how damage-associated molecular patterns (DAMPs) trigger monocyte/macrophage recruitment and activation in joints provide opportunities for disease-modifying therapies. However, the complexity and plasticity of macrophage phenotypes that exist in vivo have thus far prevented the successful development of macrophage-targeted treatments. Current studies show that synovial macrophages are derived from distinct cellular lineages, which correspond to unique functional roles for maintaining joint homeostasis. An improved understanding of the aetiology of synovial inflammation in specific OA-subtypes, such as with obesity or genetic risk, is a potential strategy for developing patient selection criteria for future precision therapies.


Asunto(s)
Macrófagos/inmunología , Osteoartritis , Sinovitis , Humanos , Inflamación , Monocitos , Osteoartritis/inmunología , Osteoartritis/patología , Sinovitis/inmunología , Sinovitis/patología
6.
Clin Exp Rheumatol ; 37 Suppl 120(5): 48-56, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31621566

RESUMEN

Osteoarthritis (OA) is the most common age-related chronic and disabling joint disease. Long considered to be a "wear and tear" disease, OA is now seen as a low-grade inflammation disease that affects all tissues of the joint, involving cartilage degradation, bone remodelling, osteophytes, and synovitis. The process, called inflammaging, is characterised by the association of low-grade inflammation, profound changes in intra-cellular mechanisms, and the decreased efficiency of the immune system with ageing. The activation of innate immunity plays a critical role in the development and progression of OA. Innate immunity, including inflammasome activation, is triggered by small endogenous molecules called alarmins or damage-associated molecular patterns (DAMPs). These molecules are released in the extracellular media after cell stress or damage, bind to pathogen-recognition receptors (PRRs), such as Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE), and activate the secretion of pro-inflammatory factors, leading to joint inflammation. Moreover, such sterile inflammation triggers cell senescence, characterised by a senescence-associated secretory phenotype (SASP). Understanding the substantial age-related changes of joint tissues that influence the pathogenesis of OA is critical to improving the quality of life of elderly people in the context of increased life expectancy. This review will focus on age-related sterile inflammation in OA and highlight the various innovative and promising therapies targeting the mechanisms of aging.


Asunto(s)
Osteoartritis , Calidad de Vida , Anciano , Envejecimiento , Humanos , Inflamación/inmunología , Osteoartritis/inmunología , Osteoartritis/patología , Osteoartritis/terapia , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptores Toll-Like/metabolismo
7.
Clin Exp Rheumatol ; 37 Suppl 120(5): 7-17, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31621569

RESUMEN

Osteoarthritis (OA) may be associated with substantial work disability, morbidity, costs, and increased mortality rates, often similar to rheumatoid arthritis (RA), documented in many published reports over the last 4 decades. However, OA generally has been viewed as less severe than RA. This discrepancy may be explained in part by:a) RA may have been considerably more severe in the past, prior to effective therapies.b) most older individuals have radiographic joint damage, which often is not associated with clinical symptoms.c) RA is associated with abnormal laboratory tests, which are regarded as conveying greater significance than symptoms of pain and disability according to a "biomedical model," the dominant paradigm of modern medicine.d) Most reports of OA and RA have emphasised differences between the 2 diseases even beyond laboratory abnormalities in pathogenesis, physical findings, and imaging.e) Even pain and functional disability seen in both diseases are assessed using different patient self-report questionnaires, a WOMAC (Western Ontario McMaster Universities osteoarthritis index) in OA, and HAQ (health assessment questionnaire) in RA.An identical measure is required for optimal direct comparisons, which has been used in 8 studies performed between 1979 and 2019 at 8 sites in North America, Europe, and Australia. These studies were primarily based on retrospective analyses at sites which collected a patient questionnaire in routine clinical care by all patients at all visits to inform clinical decisions. A pain visual analogue scale (VAS) was higher in OA compared to RA in 11/12 patient groups, while physical function on a HAQ (health assessment questionnaire) or derivative MDHAQ (multidimensional HAQ) and RAPID3 (routine assessment of patient index data) were slightly higher in RA before 2013 and higher in OA in later reports. Furthermore, a study of population-based data from the 1978 US Health Interview Survey indicated similar levels of disability and earnings losses according to surrogate variables for OA and RA. Therefore, at least over the last 40 years, pain and functional disability in OA have appeared to be severe and similar to RA. These observations also-illustrate the potential value of using an identical patient questionnaire in all patients at all visits in routine care settings, analogous to using the same laboratory tests such as erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) in all rheumatic diseases, and maintaining a database of the results for later analyses.


Asunto(s)
Artritis Reumatoide , Osteoartritis , Artritis Reumatoide/patología , Humanos , Osteoartritis/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios
8.
Am J Orthod Dentofacial Orthop ; 156(4): 531-544, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31582125

RESUMEN

Progressive condylar resorption, also known as idiopathic condylar resorption, is an uncommon, aggressive, degenerative disease of the temporomandibular joint (TMJ) seen mostly in adolescent girls and young women. This condition leads to loss of condylar bone mass, decrease of mandibular ramal height, steep mandibular and occlusal plane angles, and an anterior open bite. In 3 case reports, we review the pathogenesis of TMJ degenerative disease and the clinical management of TMJ arthrosis. We emphasize that TMJ arthritic disease should be discussed in dental circles as a pathologic entity in the same way that orthodontists discuss arthritic disease in orthopedic circles. Regarding the degenerative pathology of the TMJ, treatment goals include restored function and pain reduction. The treatment methods used to achieve these goals can range from noninvasive therapy to minimally invasive and invasive surgery. Most patients can be treated noninvasively, and the importance of disease prevention and conservative management in the overall treatment of TMJ disease must be acknowledged. The decision to manage TMJ osteoarthrosis surgically must be based on evaluation of the patient's response to noninvasive treatments, mandibular form and function, and effect of the condition on his or her quality of life.


Asunto(s)
Resorción Ósea/diagnóstico por imagen , Resorción Ósea/cirugía , Ortodoncia Correctiva/métodos , Procedimientos Quirúrgicos Ortognáticos/métodos , Osteoartritis/diagnóstico por imagen , Osteoartritis/cirugía , Trastornos de la Articulación Temporomandibular/diagnóstico por imagen , Trastornos de la Articulación Temporomandibular/terapia , Adulto , Resorción Ósea/patología , Niño , Terapia Combinada , Progresión de la Enfermedad , Femenino , Humanos , Cóndilo Mandibular/patología , Cóndilo Mandibular/cirugía , Osteoartritis/patología , Calidad de Vida , Trastornos de la Articulación Temporomandibular/patología , Resultado del Tratamiento
9.
Medicine (Baltimore) ; 98(40): e17336, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31577728

RESUMEN

Lumbar 3-joint complex degeneration is a multifactorial, pathological process. Previous studies included insufficient quantitative analyses to prove the relationship between disc degeneration and facet joint osteoarthritis (OA). We assessed the correlation between intervertebral disc and lumbar facet joint degeneration using computed tomography (CT) and magnetic resonance imaging (MRI) parameters.A total of 152 participants who underwent conventional MRI and CT in the clinostat position were included in this study. The presence of lumbar disc degeneration was identified using the Pfirrmann grading system, and the presence of lumbar facet joint degeneration was identified using the Weishaupt grading system. Facet tropism was defined as a divergence more than 7° between the facet joint angles of both sides at the same segment. The intervertebral disc heights were also measured.Most facet joint OA probably appeared at the segment with intervertebral disc degeneration of more than grade III. Facet joint OA was significantly exacerbated with the progression of disc degeneration grade. The intervertebral height significantly decreased with the progression of facet joint degeneration grades, except for grades 0 and 1.Our current study found that each individual joint degeneration influences the other 2 in the lumbar 3-joint complex. Facet tropism was significantly associated with lumbar disc degeneration. Narrowing of the intervertebral disc height probably aggravates the facet joint degeneration further at the same level.


Asunto(s)
Degeneración del Disco Intervertebral/diagnóstico por imagen , Vértebras Lumbares/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Articulación Cigapofisaria/diagnóstico por imagen , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Disco Intervertebral/patología , Degeneración del Disco Intervertebral/complicaciones , Degeneración del Disco Intervertebral/patología , Vértebras Lumbares/patología , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Osteoartritis/complicaciones , Osteoartritis/patología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tomografía Computarizada por Rayos X/métodos , Adulto Joven , Articulación Cigapofisaria/patología
10.
Orthopade ; 48(11): 949-956, 2019 Nov.
Artículo en Alemán | MEDLINE | ID: mdl-31515589

RESUMEN

Calcification in hyaline and fibrocartilage is caused by the deposition of calcium pyrophosphate dehydrate, commonly referred to as chondrocalcinosis. Clinically, this can lead to arthritis symptoms similar to a gout attack -"pseudogout". Nonetheless, also chronic or asymptomatic disease courses are possible. The prevalence of chondrocalcinosis increases with age. The diagnostic workup of degenerative joint disease, therefore, often reveals calcifications of articular cartilage as harmless incidental findings. However, particularly in patients younger than 60 years of age, chondrocalcinosis can be the symptom of an underlying metabolic disease. This review article highlights these rare diseases and presents unusual manifestations of chondrocalcinosis.


Asunto(s)
Pirofosfato de Calcio/metabolismo , Condrocalcinosis/diagnóstico , Cartílago Articular/metabolismo , Cartílago Articular/patología , Humanos , Articulaciones/patología , Persona de Mediana Edad , Osteoartritis/patología , Enfermedades Raras
11.
Life Sci ; 236: 116861, 2019 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-31513815

RESUMEN

Osteoarthritis is a prevalent worldwide joint disease, which demonstrates a remarkable adverse effect on the patients' life modality. Medicinal agents, exclusively nonsteroidal anti-inflammatory drugs (NSAIDs), have been routinely applied in the clinic. But, their effects are restricted to pain control with insignificant effects on cartilage renovation, which would finally lead to cartilage destruction. In the field of regenerative medicine, many researchers have tried to use stem cells to repair tissues and other human organs. However, in recent years, with the discovery of extracellular microvesicles, especially exosomes, researchers have been able to offer more exciting alternatives on the subject. Exosomes and microvesicles are derived from different types of bone cells such as mesenchymal stem cells, osteoblasts, and osteoclasts. They are also recognized to play substantial roles in bone remodeling processes including osteogenesis, osteoclastogenesis, and angiogenesis. Specifically, exosomes derived from a mesenchymal stem cell have shown a great potential for the desired purpose. Exosomal products include miRNA, DNA, proteins, and other factors. At present, if it is possible to extract exosomes from various stem cells effectively and load certain products or drugs into them, they can be used in diseases, such as rheumatoid arthritis, osteoarthritis, bone fractures, and other diseases. Of course, to achieve proper clinical use, advances have to be made to establish a promising regenerative ability for microvesicles for treatment purposes in the orthopedic disorders. In this review, we describe the exosomes biogenesis and bone cell derived exosomes in the regenerate process of bone and cartilage remodeling.


Asunto(s)
Cartílago Articular/citología , Exosomas/trasplante , Osteoartritis/terapia , Osteogénesis , Células Madre/citología , Humanos , Osteoartritis/complicaciones , Osteoartritis/patología , Medicina Regenerativa
12.
Cell Mol Biol (Noisy-le-grand) ; 65(6): 91-95, 2019 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-31472053

RESUMEN

Osteoarthritis (OA) is a degenerative joint disease usually seen in the elderly, which incidence increases with age. Its pathogenesis and underlying mechanism are still unclear. The disease severely affects the physical health and life quality of patients, thereby constituting a huge economic burden to family and society. Luteolin (LUT) is a natural flavonoid with multiple pharmacological properties. Many plants containing LUT have been applied in the treatment of several inflammation-related diseases due the relatively strong anti-inflammatory effects of LUT. The present study investigated the influence of LUT on cell apoptosis and inflammatory reactions in cartilage of OA guinea pigs, and its underlying mechanism. It was found that LUT effectively inhibited proliferation of OA cartilage cells, down-regulated the expressions of JNK and p38MAPK in cartilage cells of OA, and downregulated NO, TNF-α and IL-6. Thus, it alleviated inflammatory reactions, protected cartilage cells, and delayed cartilage degeneration.


Asunto(s)
Apoptosis/efectos de los fármacos , Condrocitos/enzimología , Condrocitos/patología , Luteolina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Osteoartritis/enzimología , Osteoartritis/patología , Animales , Huesos/patología , Cartílago/patología , Proliferación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Cobayas , Inflamación/patología , Mediadores de Inflamación/metabolismo , Articulaciones/patología , Lipopolisacáridos , Luteolina/química
13.
J Biosci ; 44(4)2019 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-31502578

RESUMEN

Chondrosenescence (chondrocyte senescence) and subchondral bone deterioration in osteoarthritic rats were analyzed after treatment with the estrogenic herb Labisia pumila (LP) or diclofenac. Osteoarthritis (OA) was induced in bilaterally ovariectomized (OVX) rats by injecting mono-iodoacetate into the right knee joints. Rats were grouped (n = 8) into nontreated OVX+OA control, OVX+OA + diclofenac (5 mg/kg) (positive control), OVX+OA + LP leaf extract (150 and 300 mg/kg) and healthy sham control. After 8 weeks' treatment, their conditions were evaluated via serum biomarkers, knee joint histology, bone histomorphometry, protein and mRNA expressions. The LP significantly reduced cartilage erosion, femur bone surface alteration, bone loss and porosity and increased trabecular bone thickness better than diclofenac and the non-treated OA. The cartilage catabolic markers' (matrix metalloproteinase (MMP)-13, RUNX2, COL10a, ERa, CASP3 and HIF-2 alpha) mRNA expressions were down-regulated and serum bone formation marker, PINP, was increased by LP in a dose-dependent manner. The LP (containing myricetin and gallic acid) showed protection against chondrosenescence, chondrocyte death, hypoxia-induced cartilage catabolism and subchondral bone deterioration. The bone and cartilage protective effects were by suppressing proteases (collagen break-down), bone resorption and upregulating subchondral bone restoration. The cartilage ER alpha over-expression showed a strong positive correlation with MMP-13, COL10 alpha1, histological, micro-computed tomography evidence for cartilage degradation and chondrosenescence.


Asunto(s)
Envejecimiento/efectos de los fármacos , Receptor alfa de Estrógeno/genética , Osteoartritis/tratamiento farmacológico , Extractos Vegetales/farmacología , Primulaceae/química , Envejecimiento/genética , Animales , Desarrollo Óseo/efectos de los fármacos , Cartílago/efectos de los fármacos , Cartílago/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Diclofenaco/farmacología , Modelos Animales de Enfermedad , Flavonoides/farmacología , Ácido Gálico/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Yodoacetatos/farmacología , Metaloproteinasa 13 de la Matriz/genética , Metabolismo/efectos de los fármacos , Osteoartritis/genética , Osteoartritis/patología , Ovariectomía , Extractos Vegetales/química , Ratas
14.
Cochrane Database Syst Rev ; 9: CD012958, 2019 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-31476270

RESUMEN

BACKGROUND: Chronic inflammatory joint diseases (IJDs) affect 1% to 2% of the population in developed countries. IJDs include rheumatoid arthritis (RA), ankylosing spondylitis (AS), psoriatic arthritis (PsA), and other forms of spondyloarthritis (SpA). Tobacco smoking is considered a significant environmental risk factor for developing IJDs. There are indications that smoking exacerbates the symptoms and worsens disease outcomes. OBJECTIVES: The objective of this review was to investigate the evidence for effects of smoking cessation interventions on smoking cessation and disease activity in smokers with IJD. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), the Cochrane Library; PubMed/MEDLINE; Embase; PsycINFO; the Cumulative Index to Nursing and Allied Health Literature (CINAHL); and three trials registers to October 2018. SELECTION CRITERIA: We included randomised controlled trials testing any form of smoking cessation intervention for adult daily smokers with a diagnosis of IJD, and measuring smoking cessation at least six months after baseline. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures as expected by Cochrane. MAIN RESULTS: We included two studies with 57 smokers with a diagnosis of rheumatoid arthritis (RA). We identified no studies including other IJDs. One pilot study compared a smoking cessation intervention specifically for people with RA with a less intensive, generic smoking cessation intervention. People included in the study had a mean age of 56.5 years and a disease duration of 7.7 years (mean). The second study tested effects of an eight-week cognitive-behavioural patient education intervention on cardiovascular disease (CVD) risk for people with RA and compared this with information on CVD risk only. The intervention encouraged participants to address multiple behaviours impacting CVD risk, including smoking cessation, but did not target smoking cessation alone. People included in the study had a mean age of 62.2 years (intervention group) and 60.8 years (control group), and disease duration of 11.6 years (intervention group) and 14.1 years (control group). It was not appropriate to perform a meta-analysis of abstinence data from the two studies due to clinical heterogeneity between interventions. Neither of the studies individually provided evidence to show benefit of the interventions tested. Only one study reported on adverse effects. These effects were non-serious, and numbers were comparable between trial arms. Neither of the studies assessed or reported disease activity or any of the predefined secondary outcomes. We assessed the overall certainty of evidence as very low due to indirectness, imprecision, and high risk of detection bias based on GRADE. AUTHORS' CONCLUSIONS: We found very little research investigating the efficacy of smoking cessation intervention specifically in people with IJD. Included studies are limited by imprecision, risk of bias, and indirectness. Neither of the included studies investigated whether smoking cessation intervention reduced disease activity among people with IJD. High-quality, adequately powered studies are warranted. In particular, researchers should ensure that they measure disease markers and quality of life, in addition to long-term smoking cessation.


Asunto(s)
Artritis Infecciosa/patología , Artritis Reumatoide/patología , Artropatías/patología , Cese del Hábito de Fumar/métodos , Fumar/efectos adversos , Terapia Cognitivo-Conductual , Humanos , Osteoartritis/patología , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Espondiloartritis/patología
15.
Molecules ; 24(16)2019 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-31426440

RESUMEN

Matrix metalloproteinases (MMPs) are a family of zinc- and calcium-dependent endopeptidases which are secreted or anchored in the cell membrane and are capable of degrading the multiple components of the extracellular matrix (ECM). MMPs are frequently overexpressed or highly activated in numerous human diseases. Owing to the important role of MMPs in human diseases, many MMP inhibitors (MMPIs) have been developed as novel therapeutics, and some of them have entered clinical trials. However, so far, only one MMPI (doxycycline) has been approved by the FDA. Therefore, the evaluation of the activity of a specific subset of MMPs in human diseases using clinically relevant imaging techniques would be a powerful tool for the early diagnosis and assessment of the efficacy of therapy. In recent years, numerous MMPIs labeled imaging agents have emerged. This article begins by providing an overview of the MMP subfamily and its structure and function. The latest advances in the design of subtype selective MMPIs and their biological evaluation are then summarized. Subsequently, the potential use of MMPI-labeled diagnostic agents in clinical imaging techniques are discussed, including positron emission tomography (PET), single-photon emission computed tomography (SPECT) and optical imaging (OI). Finally, this article concludes with future perspectives and clinical utility.


Asunto(s)
Aterosclerosis/diagnóstico por imagen , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Inhibidores de la Metaloproteinasa de la Matriz/farmacocinética , Metaloproteinasas de la Matriz/química , Sondas Moleculares/farmacocinética , Neoplasias/diagnóstico por imagen , Osteoartritis/diagnóstico por imagen , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Enfermedades Cardiovasculares/metabolismo , Enfermedades Cardiovasculares/patología , Dominio Catalítico/genética , Modelos Animales de Enfermedad , Encefalomielitis Autoinmune Experimental/diagnóstico por imagen , Encefalomielitis Autoinmune Experimental/metabolismo , Encefalomielitis Autoinmune Experimental/patología , Matriz Extracelular/metabolismo , Matriz Extracelular/patología , Humanos , Enfermedades Pulmonares/metabolismo , Enfermedades Pulmonares/patología , Inhibidores de la Metaloproteinasa de la Matriz/síntesis química , Metaloproteinasas de la Matriz/genética , Metaloproteinasas de la Matriz/metabolismo , Imagen Molecular/métodos , Sondas Moleculares/síntesis química , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Neoplasias/metabolismo , Neoplasias/patología , Osteoartritis/metabolismo , Osteoartritis/patología , Tomografía de Emisión de Positrones/métodos , Tomografía Computarizada de Emisión de Fotón Único/métodos
16.
Orthop Clin North Am ; 50(4): 529-537, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31466668

RESUMEN

Ankle osteoarthritis affects a significant portion of the global adult population. Unlike other joints, arthritis of the ankle often develops as a response to traumatic injury (intra-articular fracture) of the ankle joints. The full mechanism leading to posttraumatic osteoarthritis of the ankle (PTOAA) is poorly understood. These deficits in knowledge pose challenges in the management of the disease. Adequate surgical reduction of fractured ankle joints remains the gold standard in prevention. The purpose of this review is to thoroughly delineate the known pathogenesis of PTOAA, and provide critical updates on this pathology and new avenues to provide therapeutic management of the disease.


Asunto(s)
Fracturas de Tobillo/complicaciones , Fracturas de Tobillo/cirugía , Osteoartritis/patología , Fracturas de Tobillo/metabolismo , Fenómenos Biomecánicos , Manejo de la Enfermedad , Fijación Interna de Fracturas/instrumentación , Humanos , Metabolismo de los Lípidos , Osteoartritis/metabolismo , Resultado del Tratamiento
17.
Biomed Res Int ; 2019: 7165406, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31467907

RESUMEN

Early detection and treatment are critical in the management of osteoarthritis (OA). OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for the diagnosis and prognosis in OA. In this study, we aimed to explore the clinical significance of miR-210 in synovial fluid samples from 10 healthy volunteers and 20 early-stage OA and 20 late-stage OA patients. miR-210 expression was assessed by real-time RT-PCR. VEGF protein levels were examined by ELISA. The results show that miR-210 is significantly upregulated in early-stage OA and late-stage OA patients compared with healthy individuals. Higher levels of VEGF are also found in OA compared with the control. Moreover, miR-210 levels are positively correlated with VEGF levels, suggesting that miR-210 might contribute to OA development through promoting VEGF expression and angiogenesis. In conclusion, upregulation of miR-210 in synovial fluid may occur in the early stage of OA and can be a useful biomarker for early diagnosis of OA.


Asunto(s)
Biomarcadores/metabolismo , Diagnóstico Precoz , MicroARNs/genética , Osteoartritis/diagnóstico , Anciano , MicroARN Circulante , Femenino , Regulación de la Expresión Génica/genética , Humanos , Masculino , Persona de Mediana Edad , Osteoartritis/genética , Osteoartritis/patología , Líquido Sinovial/metabolismo
18.
Mol Cell Biochem ; 461(1-2): 183-193, 2019 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-31435813

RESUMEN

Osteoarthritis (OA) has been identified to be one of the most prevalent forms of joint disorders, marked with inflammatory immune response that may give rise to several complications including disability. Numbers of investigations have proven that microRNA play a key role in chondrogenesis regulation. Accordingly, the current study was intended to explore more about the potential role of miR-940 in the regulation of immune response, pertaining to osteoarthritis. Our findings indicated miR-940 associated down-regulation in both, the tissue as well as at cellular levels, i.e. chondrocytes that are being induced with IL-1ß. However, the expression of MyD88 was found to be opposite. Moreover, our findings indicated that miR-940 targets MyD88 to regulate its expression. The study was based on the proposition that normal human chondrocytes when induced with IL-1ß significantly enhanced the level of inflammation along with simultaneous stimulation of NF-κB signaling mechanism. Alternatively, siRNA against MyD88, miR-940 mimic or the NF-κB inhibitor, reversed the effect of IL-1ß. The chondrocytes that were transfected with miR-940 inhibitor increased the secretion of inflammatory cytokines and activated NF-κB. Furthermore, the expression of miR-490 was reduced in vivo, which was increased through an injection of lentivirus, to foster the production of necessary cytokines and NF-κB and the down-regulation of MyD88. In conclusion, the pathogenesis of OA can be regulated by miR-940/MyD88 axis, which can be achieved through the combined signaling mechanism of MyD88/NF-κB signaling, induced with the help of IL-1ß.


Asunto(s)
Condrocitos/metabolismo , Condrocitos/patología , Inflamación/genética , MicroARNs/metabolismo , Factor 88 de Diferenciación Mieloide/metabolismo , Osteoartritis/genética , Regiones no Traducidas 3'/genética , Adulto , Anciano , Animales , Secuencia de Bases , Proliferación Celular , Citocinas/metabolismo , Femenino , Regulación de la Expresión Génica , Humanos , Inflamación/patología , Interleucina-1beta/metabolismo , Masculino , MicroARNs/genética , Persona de Mediana Edad , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/metabolismo , Osteoartritis/patología , Ratas , Transducción de Señal
19.
Life Sci ; 234: 116786, 2019 Oct 01.
Artículo en Inglés | MEDLINE | ID: mdl-31445934

RESUMEN

Extensive degeneration of articular cartilage (AC) is a primary event in the pathogenesis of osteoarthritis (OA) and other types of joint and bone inflammation. OA results in the loss of joint function, usually accompanied by severe pain, and are the most common type of arthritis, affecting more than 10% of adults. The characteristic signs of OA are progressive cartilage destruction and, eventually, complete loss of chondrocytes. A key enzyme responsible for these degenerative changes in cartilage is matrix metalloproteinase-13 (MMP-13), which is thought to be a major contributor to the degenerative process occurring during OA pathogenesis. The aim of the present review is to shed light on the general role of MMPs, with special emphasis on MMP-13, in the induction of OA and the general basis of OA treatment. The pathogenic mechanism of this highly prevalent disease is not clear, and no effective disease-modifying treatment is currently available. Any updated information about OA treatment in human patients will also benefit companion animals such as horses and dogs, which also suffer from OA. Selective inhibition of MMP-13 seems to be an attractive therapeutic strategy.


Asunto(s)
Cartílago Articular/patología , Matriz Extracelular/patología , Metaloproteinasas de la Matriz/inmunología , Osteoartritis/patología , Animales , Cartílago Articular/efectos de los fármacos , Cartílago Articular/inmunología , Cartílago Articular/metabolismo , Descubrimiento de Drogas , Matriz Extracelular/efectos de los fármacos , Matriz Extracelular/inmunología , Matriz Extracelular/metabolismo , Humanos , Metaloproteinasa 13 de la Matriz/análisis , Metaloproteinasa 13 de la Matriz/inmunología , Metaloproteinasa 13 de la Matriz/metabolismo , Inhibidores de la Metaloproteinasa de la Matriz/farmacología , Inhibidores de la Metaloproteinasa de la Matriz/uso terapéutico , Metaloproteinasas de la Matriz/análisis , Metaloproteinasas de la Matriz/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/inmunología , Osteoartritis/metabolismo
20.
Artif Cells Nanomed Biotechnol ; 47(1): 3239-3245, 2019 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-31364869

RESUMEN

Osteoarthritis (OA) is a major public health concern for which a reliable non-invasive treatment option has yet to be developed. In the present study, we investigated the effects of saxagliptin, a novel dipeptidyl peptidase IV (DPP-4) inhibitor, on several important aspects of the pathophysiology of OA using primary human chondrocytes. The results of real-time PCR and ELISA analyses show that saxagliptin treatment significantly decreased mRNA and protein expression of three key cartilage degrading enzymes: matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13. The results of western blot confirmed that this decrease in MMP-1, -3, and -13 expression prevented degradation of type II collagen. We also found that saxagliptin significantly inhibited expression of a disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-4 and ADAMTS-5, which was reflected by markedly decreased degradation of aggrecan. Inhibition of DPP-4 by saxagliptin also reduced oxidative stress in human primary chondrocytes as evidenced by decreased production of reactive oxygen species (ROS) and increased glutathione (GSH) levels. Additionally, the results of western blot analysis show that the effects of saxagliptin are mediated through the p38/IκBα/NF-κB pathway, which is considered an important treatment target for OA. These findings suggest a potential role for saxagliptin as a novel treatment against OA.


Asunto(s)
Adamantano/análogos & derivados , Agrecanos/metabolismo , Condrocitos/efectos de los fármacos , Condrocitos/metabolismo , Colágeno Tipo II/metabolismo , Dipéptidos/farmacología , Osteoartritis/tratamiento farmacológico , Proteolisis/efectos de los fármacos , Proteína ADAMTS4/metabolismo , Proteína ADAMTS5/metabolismo , Adamantano/farmacología , Adamantano/uso terapéutico , Condrocitos/patología , Dipéptidos/uso terapéutico , Progresión de la Enfermedad , Activación Enzimática/efectos de los fármacos , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Productos Finales de Glicación Avanzada/farmacología , Humanos , Metaloproteinasas de la Matriz/metabolismo , Inhibidor NF-kappaB alfa/metabolismo , FN-kappa B/metabolismo , Osteoartritis/metabolismo , Osteoartritis/patología , Especies Reactivas de Oxígeno/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
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