HYPERPOLARIZATION OF CULTURED HUMAN CHONDROCYTES FOLLOWING CYCLICAL PRESSURE-INDUCED STRAIN - EVIDENCE OF A ROLE FOR ALPHA-5-BETA-1 INTEGRIN AS A CHONDROCYTE MECHANORECEPTOR

Mechanical stimuli influence chondrocyte metabolism, inducing changes in intracellular cyclic adenosine monophosphate and proteoglycan produ ction. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after int ermittent pressure-induced strain characterised by a membrane hyperpol arisation of approximately 40%. The mechanisms responsible far these c hanges are not fully understood but potentially involve signalling mol ecules such as integrins that link extracellular matrix with cytoplasm ic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of h uman articular chondrocytes in vitro after cyclical pressure-induced s train involve alpha 5 beta 1 integrin, We have demonstrated, using pha rmacological inhibitors of a variety of intracellular signalling pathw ays. that the actin cytoskeleton, the phospholipase C calmodulin pathw ay, and both tyrosine protein kinase and protein kinase C activities a re important in the transduction of the electrophysiological response. These results suggest that alpha 5 beta 1 is an important chondrocyte mechanoreceptor and a potential regulator of chondrocyte function.