Altered electrophysiological responses to mechanical stimulation and abnormal signalling through alpha 5 beta 1 integrin in chondrocytes from osteoarthritic cartilage

Objective: To establish whether chondrocytes from normal and osteoarthritic human articular cartilage recognize and respond to pressure induced mechan ical strain in a similar manner. Design. Chondrocytes, extracted from macroscopically normal and osteoarthri tic human articular cartilage obtained from knee joints at autopsy, were gr own in monolayer culture and subjected to cyclical pressure-induced strain (PIS) in the absence or presence of anti-integrin antibodies, agents known to block ion channels and inhibitors of key molecules involved in the integ rin-associated signalling pathways. The response of the cells to mechanical stimulation was assessed by measuring changes in membrane potential. Results: Unlike chondrocytes from normal articular cartilage, which showed a membrane hyperpolarization response to PIS, chondrocytes from osteoarthri tic cartilage responded by membrane depolarization. The mechanotransduction pathway involves alpha 5 beta 1 integrins, stretch-activated ion channels, tyrosine kinases and phospholipase C but the actin cytoskeleton and protei n kinase C, which are important in the membrane hyperpolarization response in normal chondrocytes, are not necessary for membrane depolarization in os teoarthritic chondrocytes in response to PIS. Conclusion: Chondrocytes derived from osteoarthritic cartilage show a diffe rent signalling pathway via alpha 5 beta 1 integrin in response to mechanic al stimulation which may be of importance in the production of phenotypic c hanges recognized to be present in diseased cartilage. (C) 2000 OsteoArthri tis Research Society International.