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The role of osteoblast AMPA receptors in stimulation of bone formation

ReferenceS18293
Principal Investigator / Supervisor Professor T M Skerry
Co-Investigators /
Co-Supervisors
Institution Royal Veterinary College
DepartmentVeterinary Basic Sciences - London
Funding typeResearch
Value (£) 239,924
StatusCompleted
TypeResearch Grant
Start date 01/10/2003
End date 31/01/2005
Duration16 months

Abstract

The most intractable problem in skeletal pathology is stimulation of bone formation after loss. In pilot studies, we discovered that surprisingly, low but not high doses of antagonists of AMPA-type glutamate receptors stimulate expression of osteoblast phenotypic markers and bone formation in vitro and in vivo. We will test the hypothesis that low doses of antagonists that bind to the thiazide- sensitive anti-desensitisation site of AMPA receptors exert agonist effects, initiating osteogenic responses. We will determine subgroups of AMPA receptors expressed in bone, marrow and osteoblasts, and the characteristics of ligand and putative antagonist binding to osteoblasts. We will also measure effects of antagonists at different doses on intracellular calcium concentration, c-fos for expression and AP-1 activity, and in vivo, on bone mass in rats after ovariectomy and in response to mechanical loading.

Summary

unavailable
Committee Closed Committee - Animal Sciences (AS)
Research TopicsX – not assigned to a current Research Topic
Research PriorityX – Research Priority information not available
Research Initiative X - not in an Initiative
Funding SchemeX – not Funded via a specific Funding Scheme
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