The ANABONOS project, Molecular Mechanisms
of Bone Formation and Anabolism:
Osteoporotic fractures are a major healthcare problem in Europe and this is
set to increase as the proportion of the elderly individuals in the population
expands. Osteoporosis can be treated by drugs that inhibit bone resorption,
but these do not restore normal skeletal strength and are incompletely effective
at preventing fractures. Consequently, there is an urgent need to develop new
treatments for osteoporosis that stimulate bone formation. Such treatments
would offer the prospect of greater efficacy by reversing the structural abnormalities
of bone in established osteoporosis. This project will advance understanding
of the mechanisms responsible for bone formation, with the long-term aim of
harnessing this knowledge to develop new anabolic agents for osteoporosis.
These aims will be achieved by drawing leading European
academic research groups together with SME’s working in bone
metabolism to define the mechanisms of bone formation and uncover
pathways that can be targeted for therapeutic intervention. We
will define downstream effectors of molecules that regulate bone
formation in mice and define signalling pathways that are activated
in human genetic diseases characterised by increased bone formation.
The mechanisms of action of drugs with known anabolic effects will
be investigated and novel genes that regulate bone formation will
be uncovered by ENU mutagenesis and genetic mapping studies.
The project will lead to a greater understanding
of how bone formation is regulated and will underpin the development
of new therapeutic strategies for the prevention and treatment
of osteoporosis.
The OSTEOGENE project is focused
on improving the understanding of the molecular mechanisms involved
in bone homeostasis. A main emphasis is on the anabolic aspects.
New knowledge is sought using contemporary array technology and
functional genomics building on the recently definition of the
human genome. A major target is identification of the mRNAs and
proteins that exercise a central role in the building (anabolic)
phases of bone metabolism, including but not limited to those regulated
by parathyroid hormone (PTH).
Selective stimulation of anabolic effectors, it is
argued, form the basis for new treatment modalities that will increase
new and fully-functional bone formation. This approach contrasts
with many contemporary regimes of treatment that primarily inhibit
bone resorption, thus increasing the amount of more or less worn
tissue. A special attempt is made to identify genetic markers that
can be used for early identification of people at risk for later
development of osteoporosis.
The project is undertaken by a multidisciplinary
team including medical practitioners, molecular and cellular biologists
and biochemists all with an international track record. The long-term
aim is a reduction in the impact of osteoporosis in Europe brought
about by application of appropriate evidence-based therapeutic
and preventive medicine.
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