Human genome-wide expression analysis reorients the study of inflammatory mediators and biomechanics in osteoarthritis.
Osteoarthritis Cartilage
; 23(11): 1939-45, 2015 Nov.
Article
em En
| MEDLINE
| ID: mdl-26521740
ABSTRACT
A major objective of this article is to examine the research implications of recently available genome-wide expression profiles of cartilage from human osteoarthritis (OA) joints. We propose that, when viewed in the light of extensive earlier work, this novel data provides a unique opportunity to reorient the design of experimental systems toward clinical relevance. Specifically, in the area of cartilage explant biology, this will require a fresh evaluation of existing paradigms, so as to optimize the choices of tissue source, cytokine/growth factor/nutrient addition, and biomechanical environment for discovery. Within this context, we firstly discuss the literature on the nature and role of potential catabolic mediators in OA pathology, including data from human OA cartilage, animal models of OA, and ex vivo studies. Secondly, due to the number and breadth of studies on IL-1ß in this area, a major focus of the article is a critical analysis of the design and interpretation of cartilage studies where IL-1ß has been used as a model cytokine. Thirdly, the article provides a data-driven perspective (including genome-wide analysis of clinical samples, studies on mutant mice, and clinical trials), which concludes that IL-1ß should be replaced by soluble mediators such as IL-17 or TGF-ß1, which are much more likely to mimic the disease in OA model systems. We also discuss the evidence that changes in early OA can be attributed to the activity of such soluble mediators, whereas late-stage disease results more from a chronic biomechanical effect on the matrix and cells of the remaining cartilage and on other local mediator-secreting cells. Lastly, an updated protocol for in vitro studies with cartilage explants and chondrocytes (including the use of specific gene expression arrays) is provided to motivate more disease-relevant studies on the interplay of cytokines, growth factors, and biomechanics on cellular behavior.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Osteoartrite
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Cartilagem Articular
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Expressão Gênica
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Genoma Humano
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Mediadores da Inflamação
Tipo de estudo:
Guideline
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Osteoarthritis Cartilage
Assunto da revista:
ORTOPEDIA
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REUMATOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article