Extracellular and intracellular mechanisms of mechanotransduction in three-dimensionally embedded rat chondrocytes.
PLoS One
; 9(12): e114327, 2014.
Article
em En
| MEDLINE
| ID: mdl-25479057
ABSTRACT
PURPOSE:
Articular cartilage homeostasis involves modulation of chondrocyte matrix synthesis in response to mechanical stress (MS). We studied extracellular and intracellular mechanotransduction pathways mediating this response.METHODS:
We first confirmed rapid up-regulation of the putative chondro-protective cytokine, interleukin (IL)-4, as an immediate response to MS. We then studied the role of IL-4 by investigating responses to exogenous IL-4 or a specific IL-4 inhibitor, combined with MS. Next we investigated the intracellular second messengers. Since chondrocyte phenotype alters according to the extracellular environment, we characterized the response to mechanotransduction in 3-dimensionally embedded chondrocytes.RESULTS:
Expression of aggrecan and type II collagen was significantly up-regulated by exogenous IL-4 whereas MS-induced matrix synthesis was inhibited by an IL-4 blocker. Further, MS-induced matrix synthesis was completely blocked by a p38 MAPK inhibitor, while it was only partially blocked by inhibitors of other putative second messengers.CONCLUSION:
IL-4 mediates an extracellular pathway of mechanotransduction, perhaps via an autocrine/paracrine loop, while p38 mediates an intracellular pathway prevalent only in a 3-dimensional environment.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Condrócitos
/
Comunicação Autócrina
/
Comunicação Parácrina
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Mecanotransdução Celular
/
Matriz Extracelular
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article