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The role of osteoblast AMPA receptors in stimulation of bone formation
Reference
S18293
Principal Investigator / Supervisor
Professor T M Skerry
Co-Investigators /
Co-Supervisors
Institution
Royal Veterinary College
Department
Veterinary Basic Sciences - London
Funding type
Research
Value (£)
239,924
Status
Completed
Type
Research Grant
Start date
01/10/2003
End date
31/01/2005
Duration
16 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 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
Associated awards:
S18293/2 The role of osteoblast AMPA receptors in stimulation of bone formation
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