Objective. To study the changes in patterns of gene expression exhibited by human chondrocytes as they dedifferentiate into fibroblastic cells in culture in order to better understand the mechanisms that control this process and its relationship to the phenotypic changes that occur in chondrocytes during the development of osteoarthritis (OA).Methods. Human fetal epiphyseal chondrocytes (HFCs) were cultured either on poly-(2-hydroxyethyl methacrylate)-coated plates (differentiated HFC cultures) or in plastic tissue culture flasks as monolayers (dedifferentiated HFC cultures). Following 11 days of culture under either condition, poly(A؉) RNA was isolated from the two cell populations and subjected to a gene expression analysis using a microarray containing ϳ5,000 known human genes and ϳ3,000 expressed sequence tags (ESTs).Results. A >2-fold difference in the expression of 62 known genes and 6 ESTs was observed between the two cell types. The differences in expression of several of the genes detected by the microarray hybridization were confirmed by Northern analyses. Two transcription factor genes, TWIST and HIF-1␣, and a cellular adhesion protein gene, cadherin 11, were markedly regulated in response to differentiation and dedifferentiation. Expression of these genes was also detected in adult normal and OA cartilage and chondrocytes. Analysis of the gene expression profile of HFCs revealed a complex pattern of gene expression, including many genes not yet reported to be expressed by chondrocytes.Conclusion. Chondrocytes in monolayer become dedifferentiated, acquiring a fibroblast-like appearance and changing their pattern of gene expression from one of expression of chondrocyte-specific genes to one that resembles a fibroblastic or chondroprogenitor-like pattern. Changes in gene expression associated with the process of dedifferentiation of HFCs in vitro were observed in a wide variety of genes, including genes encoding extracellular matrix proteins, transcription factors, and growth factors. At least 3 of the genes that were regulated in response to dedifferentiation were also found to be expressed in adult normal and OA articular cartilage and chondrocytes.
These recommendations are based on the consensus of clinical experts from a wide range of disciplines taking available evidence into account while balancing the benefits and risks of nonpharmacological, pharmacological, and surgical treatment modalities, and incorporating their preferences and values. Different backgrounds in terms of patient education or drug availability in different countries were not evaluated but will be important.
BackgroundBody composition (BC) in the elderly has been associated with diseases and mortality; however, there is a shortage of data on frailty in the elderly.ObjectiveTo investigate the association between BC and frailty, and identify BC profiles in nonfrail, prefrail, and frail elderly people.MethodsA cross-sectional study comprising 235 elderly (142 females and 93 males) aged ≥65 years, from the city of Amparo, State of São Paulo, Brazil, was undertaken. Sociodemographic and cognitive features, comorbidities, medication, frailty, body mass index (BMI), muscle mass, fat mass, bone mass, and fat percent (%) data were evaluated. Aiming to examine the relationship between BC and frailty, the Mann–Whitney and Kruskal–Wallis nonparametric tests were applied. The statistical significance level was P<0.05.ResultsThe nonfrail elderly showed greater muscle mass and greater bone mass compared with the prefrail and frail ones. The frail elderly had greater fat % than the nonfrail elderly. There was a positive association between grip strength and muscle mass with bone mass (P<0.001), and a negative association between grip strength and fat % (P<0.001). Gait speed was positively associated with fat mass (P=0.038) and fat % (P=0.002). The physical activity level was negatively associated with fat % (P=0.022). The weight loss criterion was positively related to muscle mass (P<0.001), bone mass (P=0.009), fat mass (P=0.018), and BMI (P=0.003). There was a negative association between fatigue and bone mass (P=0.008).Discussion: Frailty in the elderly was characterized by a BC profile/phenotype with lower muscle mass and lower bone mass and with a higher fat %. The BMI was not effective in evaluating the relationship between BC and frailty. The importance of evaluating the fat % was verified when considering the tissue distribution in the elderly BC.
DESCRIÇÃO DO MÉTODO DE COLETA DE EVIDÊNCIAS: Foram utilizados os estudos disponíveis na literatura médica presentes nas seguintes bases de dados, acessíveis através da internet: OVID (EBM-Reviews, incluindo-se as bases de dados da Cochrane) e o Medline, de 1966 até o presente, através do Pubmed. Foram selecionados trabalhos de meta-análise e estudos duplo-cegos randomizados, quando presentes. Relatos ou série de casos foram utilizados quando publicados em jornaisde reconhecida idoneidade. As opiniões dos especialistas presentes foram utilizadas em relação a terapias não disponíveis na literatura e que fossem consideradas pela unanimidade dos presentes como importante para o manejo dos pacientes com osteoartrite. Envio prévio da bibliografia principal aos participantes. Reunião para elaboração do documento. Colocação do rascunho na internet por dez dias para mudanças. Elaboração final do documento. GRAU DE RECOMENDAÇÃO E FORÇA DE EVIDÊNCIA: A: Estudos experimentais e observacionais de melhor consistência. B: Estudos experimentais e observacionais de menor consistência. C: Relatos de casos (estudos não controlados). D: Opinião desprovida de avaliação crítica, baseada em consensos, estudos fisiológicos ou modelos animais. OBJETIVOS: Conciliar informações e condutas referentes ao tratamento da osteoartrite pelas três principais especialidades envolvidas, reumatologia, fisiatria e ortopedia. As condutas consensuais para a maioria dos participantes foram então agrupadas e constam nas recomendações deste documento. CONFLITO DE INTERESSE: Os autores Coimbra IB, Pucinelli MLC, Cavalcanti FS e Maciel FMB, declararam vínculo com a Indústria Farmacêutica
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