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Control of hypertrophy in mammalian growth plate chondrocytes by membrane transporters

Reference	BB/C513985/1
Principal Investigator / Supervisor	Dr Andrew Hall
Co-Investigators / Co-Supervisors
Institution	University of Edinburgh
Department	Biomedical Sciences
Funding type	Research
Value (£)	230,005
Status	Completed
Type	Research Grant
Start date	01/04/2005
End date	30/09/2008
Duration	42 months

Abstract

The regulated swelling of chondrocytes in the growth plate (termed hypertrophy) is an essential step that is crucial for the orderly and rapid lengthening of bones during development. The failure of hypertrophy is directly implicated in growth and skeletal disorders and also childhood injuries of the growth plate. However the process(es) by which chondrocytes swell is unknown. It is highly probable that the accumulation of osmolytes (especially ions) by chondrocyte membrane transporters coupled with suppression of normal volume regulatory pathways are involved. This project will utilise 2-photon laser scanning microscopy (2PLSM) to study the role of the various volume-sensitive membrane transporters of living in situ and isolated growth plate chondrocytes maintained in alginate culture and which undergo hypertrophy. By loading chondrocytes with appropriate fluorescent indicators and subjecting cells to various experimental manoeuvres and pharmacological agents, we will characterise the osmolyte transporters involved in the regulated swelling of hypertrophy. We will also use fluorescence immunohistochemistry (FI) of in situ chondrocytes along the growth plate, and this technique coupled with radiotracer flux and inhibitor binding experiments on isolated growth plate chondrocytes maintained in culture, to assess the contributions of the various membrane transporters to chondrocyte enlargement. Using 2PLSM and fluorescent dyes sensitive to intracellular ion concentrations, we will study the changes in ion concentration (calibrated where possible) along the growth plate, and in chondrocyte cultures undergoing hypertrophy. For all these measurements, chondrocytes within articular cartilage (which do not undergo the differentiation cascade) will be used as a comparative control. Overall the aim is to understand the role of osmolyte transporters controlling chondrocyte hypertrophy in the mammalian growth plate.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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