Altered electrophysiological responses to mechanical stimulation and abnormal signalling through alpha5beta1 integrin in chondrocytes from osteoarthritic cartilage.
OBJECTIVE
To establish whether chondrocytes from normal and osteoarthritic human articular cartilage recognize and respond to pressure induced mechanical strain in a similar manner.


METHODS
Chondrocytes, extracted from macroscopically normal and osteoarthritic human articular cartilage obtained from knee joints at autopsy, were grown 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 integrin-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 osteoarthritic cartilage responded by membrane depolarization. The mechanotransduction pathway involves alpha5beta1 integrins, stretch-activated ion channels, tyrosine kinases and phospholipase C but the actin cytoskeleton and protein kinase C, which are important in the membrane hyperpolarization response in normal chondrocytes, are not necessary for membrane depolarization in osteoarthritic chondrocytes in response to PIS.


CONCLUSIONS
Chondrocytes derived from osteoarthritic cartilage show a different signalling pathway via alpha5beta1 integrin in response to mechanical stimulation which may be of importance in the production of phenotypic changes recognized to be present in diseased cartilage.
Millward-Sadler
S J
SJ
Department of Pathology, University of Edinburgh Medical School, Teviot Place, Edinburgh, EH8 9AG, U.K.
Wright
M O
MO
Lee
H
H
Caldwell
H
H
Nuki
G
G
Salter
D M
DM
D000368:Aged; D000369:Aged, 80 and over; D002358:Cartilage, Articular / Q000503:physiopathology*; D002450:Cell Communication; D016764:Cell Polarity; D002478:Cells, Cultured; D019902:Chondrocytes / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D005260:Female; D006801:Humans; D007473:Ion Channels / Q000502:physiology; D008297:Male; D008564:Membrane Potentials; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000473:pathology / Q000503:physiopathology*; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology; D017469:Receptors, Fibronectin / Q000502:physiology*; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000502:physiology
D007473:Ion Channels; D017469:Receptors, Fibronectin; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases