Wnt signaling: a key regulator of bone mass.
The identification of a link between bone mass in humans and gain- [high bone mass (HBM) trait] or loss-of-function [osteoporosis pseudoglioma (OPPG) syndrome] mutations in the Wnt coreceptor lipoprotein receptor-related protein (LRP)5 or in the Wnt antagonist sclerostin (sclerosteosis, Van Buchem syndrome) has called the attention of academic and industry scientists and clinicians to the importance of this signaling pathway in skeletal biology and disease. Multiple genetic and pharmacological manipulations of Wnt signaling in mice have since then confirmed the central role of this pathway in both the establishment of peak bone mass and its maintenance throughout life. Wnt signaling appears to be located downstream of bone morphogenetic proteins (BMPs), itself induced by Hedgehog (Hh) signaling, suggesting that it is the successive recruitment of these three intracellular signaling cascades that allow the full expression of the genetic patterns that characterize the osteoblast, the cell responsible for the formation of bone.
Baron
Roland
R
Yale University School of Medicine New Haven, Connecticut 06520, USA.
Rawadi
Georges
G
Roman-Roman
Sergio
S
D000818:Animals; D015519:Bone Density; D016723:Bone Remodeling; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D026502:LDL-Receptor Related Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D008954:Models, Biological; D009154:Mutation; D010006:Osteoblasts / Q000378:metabolism; D010012:Osteogenesis; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; C555475:LRP6 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse; D051153:Wnt Proteins; D051176:beta Catenin