[Wnt/LRP5, a new regulation osteoblastic pathway involved in reaching peak bone masses]

With the ageing of the population in industrial countries, osteoporosis became an important concern of public health. For an efficacious treatment of this disease, we would need drugs capable of selectively and safely increasing bone volume. Recent genetic analyses revealed a new signaling pathway involved in the regulation of osteoblastic cells and the acquisition of pic bone mass. Loss or gain of function mutations in the LRP5 gene have been found to be associated with correspondingly low or high bone mass syndromes. Loss of function is associated with juvenile osteoporosis, whereas gain of function leads to the high bone mass syndrome. Recent studies have shown that LRP5 is implicated in the regulation of the proliferation and of the activity of osteoblastic cells. By analogy with other cellular systems, it has been suggested that LRP5 plays a role in the Wnt signaling system. Wnt proteins are known to be involved in developmental processes and the implication of this system in controlling osteoblastic activity and bone formation was completely unexpected. Analysis of the cellular mechanism by which Wnt/LRP5 activates osteoblastic cells is of potential interest for the development of new molecules capable of selectively increasing bone mass for the treatment of osteoporosis.