Objective
The balance between bone resorption and bone formation determines the mass and structural integrity of the skeleton and is disturbed in osteoporosis. In contrast to the molecular mechanisms regulating bone resorption, knowledge of the mechanisms regulating bone formation is limited. A recent breakthrough has been the identification of a link between bone mass in humans with rare bone disorders and gain- or loss-of function mutations of the Wnt co-receptor LRP5 or the Wnt antagonist sclerostin. The mechanism, however, underlying these actions on Wnt signalling is unclear. We propose studies with the following specific aims: i) to characterize the clinical, bioschemical, radiological and histological features of patients with sclerosteosis, van Buchem disease and other craniotubular hyperostoses ii) to determine the genetic defect in patients with craniotubular hyperostoses and establish putative genotype-phenotype correlations iii) to unravel the molecular mechanism of the inhibitory action of sclerostin on bone formation and to determine how genetic variations in SOST, LRP5 and Wnt signalling pathway modify bone architecture and remodelling iv) to reveal the pattern of sclerostin expression by analysis of the SOST promoter and by histomorphometry of human bone biopsies v) to identify and characterize co-factors of the LRP5 signalling and their in vivo actions in relevant animal models vi) to identify epitopes in sclerostin that mediate the interaction with LRP5, raise peptide-bound protein mimics and test them in vitro and in animal models of bone loss. These studies will not only help understanding the molecular basis of critical signalling pathway in bone formation but will also provide insight into normal and disturbed modulation of bone remodelling. Moreover, they will help in the design of bone forming interventions for the treatment of patients with osteoporosis.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- natural sciences biological sciences biochemistry biomolecules proteins
- natural sciences biological sciences genetics mutation
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-HEALTH-2007-A
See other projects for this call
Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Coordinator
2333 ZA Leiden
Netherlands
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.