Fighting osteoporosis by blocking nucleotides: purinergic signalling in bone formation and homeostasis
Coordinator: Niklas Rye JORGENSEN
Project Number: 202231
EC contribution: € 2,998,682.00
Project website: http://www.atpbone.org/
Osteoporosis is a disabling disease and the incidence is expected to increase significantly over the next decades due to an increase in the elderly population. This will lead to an enormous economical burden both in the European Union and in the rest of the world. Osteoporosis should be treated early in order to prevent the bone fractures related to the disease, and a number of anti-resorptive treatments exist that can reduce the loss of bone. However, the possibilities of regaining already lost bone are limited, as only one anabolic treatment option (parathyroid hormone (PTH) )is available on the market. In most countries PTH is restricted to the most severe cases of osteoporosis with multiple fractures. Thus new anabolic treatment options for osteoporosis are highly warranted. Purinergic signalling, where nucleotides such as ATP act as extracellular signalling molecules, is a rapidly expanding field. The purinergic system has plays a central role in bone physiology, and bone deposition and resorption are finely tuned by extracellular nucleotides. Furthermore, the "purinergic system" is now believed to be one of the main transducing pathways of mechanical stimulation, a stimulus that is highly anabolic to bone. The overall aim of the proposal is to definitively prove the role of ATP and purinergic receptor signalling in the control of bone formation and homeostasis, thereby proving the potential of the system as a target for the development of new anabolic treatment regimens for osteoporosis. The aim will be addressed by examining the role of ATP as a signalling molecule in bone, the pathways and purinergic receptors involved in the signalling and their role in bone formation and homeostasis in vitro. Furthermore, translational studies in in vivo P2 receptor knock out mice will be used to show the role of the signalling pathways on bone, as well as small-scale clinical proof-of-concept studies to prove the potential of the system in targeting osteoporosis.