Molecular bases of the regulation of bone remodeling by the canonical Wnt signaling pathway.
Osteoporosis is a common, prevalent, and debilitating condition, particularly in postmenopausal women. Genetics play a major role in determining peak bone mass and fracture risk, but few genes have been demonstrated conclusively to be involved, much less the signaling pathways with which they are affiliated. The identification of mutations in the gene Lrp5, a Wnt coreceptor, as the cause for both osteoporotic and high-bone mass disorders implicated the canonical Wnt signaling pathway in bone mass regulation. Since Lrp5, other Wnt components have been identified as being regulators of bone mass, and Wnt target genes affecting bone homeostasis have begun to be elucidated. This chapter looks at the various components of the canonical Wnt signaling pathway and the data indicating that this pathway plays a major role in the control of both bone formation and bone resorption, the two key aspects of bone remodeling.
Glass
Donald A
DA
Department of Molecular and Human Genetics, Bone Disease Program of Texas, Baylor College of Medicine, Houston, 77030, USA.
Karsenty
Gerard
G
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D060466:Axin Protein; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D016723:Bone Remodeling / Q000502:physiology*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D051157:Frizzled Receptors / Q000378:metabolism; D005819:Genetic Markers; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins / Q000378:metabolism; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008565:Membrane Proteins / Q000378:metabolism; D010024:Osteoporosis / Q000378:metabolism / Q000503:physiopathology; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D015398:Signal Transduction / Q000502:physiology*; D051820:TCF Transcription Factors / Q000378:metabolism; D051153:Wnt Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D060466:Axin Protein; D019485:Bone Morphogenetic Proteins; D003598:Cytoskeletal Proteins; D051157:Frizzled Receptors; D005819:Genetic Markers; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D008565:Membrane Proteins; D020794:Receptor Protein-Tyrosine Kinases; D057050:Receptor Tyrosine Kinase-like Orphan Receptors; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; C491761:AXIN2 protein, human; C486077:Kremen1 protein, mouse; C555482:LRP5 protein, human; C555475:LRP6 protein, human; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse; C486030:Sost protein, mouse; C477010:Ror2 protein, mouse