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Title: Volume regulation by articular chondrocytes
Author: Kerrigan, Mark John Patrick
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2003
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For isolated chondrocytes (avian, bovine and human) and in response to a decrease in extracellular osmolality there was an increase in cell volume and some cells underwent Regulatory Volume Decrease (RVD). It was found that RVD did not appear to depend upon the polymerisation state of actin (bovine chondrocytes); not dependent upon gadolinium-sensitive, stretch-activated ion channels (avian, bovine and human chondrocytes); but was inhibited by REV 5901 (avian and bovine chondrocytes). Conversely, an increase in extracellular osmolality resulted in cell shrinkage where there was an absence of any significant Regulatory Volume Increase (RVI) despite the expression of the Na-K-2Cl co-transporter. Isolating the chondrocytes into a lower osmolality, or the post RVD-RVI protocol, did not significantly increase the number of cells showing RVI. Both hypo and hyper-osmotic challenges resulted in an increase in [Ca2+]i that did not correlate with the capacity for volume regulation. When comparing the capacity for RVD between chondrocytes isolated from macroscopically ‘degenerate’ and ‘non-degenerate’ human articular cartilage no differnces were found. These data show that freshly isolated chondrocytes have the capacity for RVD but not RVI. RVD is mediated though an actin independent, gadolinium insensitive, osmolyte channel and is not dependent upon a rise in [Ca2+]i. The lack of RVI may be attributed to the diurnal, cyclic hydration and dehydration of cartilage as the extracellular osmolality will return towards the ‘resting’ value as cartilage re-hydrates when it is unloaded. Despite the fact chondrocytes isolated form ‘degenerate’ cartilage were able to perform RVD, previous work has shown an increase in resting chondrocyte volume with advancing OA. The present work identifies some of the characteristics and signalling pathways for volume regulatory behaviour by articular chondrocytes exposed to anisotonic conditions. The role played by these pathways in the maintenance of volume homeostasis by chondrocytes within non-degenerate cartilage, and how these might be perturbed in the degenerative process of OA are discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available