Hyperpolarisation 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 production. We have previously demonstrated that primary monolayer cultures of human chondrocytes have an electrophysiological response after intermittent pressure-induced strain characterised by a membrane hyperpolarisation of approximately 40%. The mechanisms responsible for these changes are not fully understood but potentially involve signalling molecules such as integrins that link extracellular matrix with cytoplasmic components. The results reported in this paper demonstrate that the transduction pathways involved in the hyperpolarisation response of human articular chondrocytes in vitro after cyclical pressure-induced strain involve alpha 5 beta 1 integrin. We have demonstrated, using pharmacological inhibitors of a variety of intracellular signalling pathways, that the actin cytoskeleton, the phospholipase C calmodulin pathway, and both tyrosine protein kinase and protein kinase C activities are 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.
Wright
M O
MO
Department of Physiology, University of Edinburgh Medical School, Scotland.
Nishida
K
K
Bavington
C
C
Godolphin
J L
JL
Dunne
E
E
Walmsley
S
S
Jobanputra
P
P
Nuki
G
G
Salter
D M
DM
D000199:Actins / Q000378:metabolism; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism*; D004594:Electrophysiology; D006801:Humans; D019012:Integrin beta1 / Q000494:pharmacology; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects; D009842:Oligopeptides / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D017469:Receptors, Fibronectin / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D013314:Stress, Mechanical; D010738:Type C Phospholipases / Q000378:metabolism
D000199:Actins; D019012:Integrin beta1; D009842:Oligopeptides; D017469:Receptors, Fibronectin; C101396:glycyl-arginyl-alanyl-aspartyl-seryl-proline; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010738:Type C Phospholipases