In vivo analysis of Wnt signaling in bone.
Bone remodeling requires osteoblasts and osteoclasts working in concert to maintain a constant bone mass. The dysregulation of signaling pathways that affect osteoblast or osteoclast differentiation or function leads to either osteopenia or high bone mass. The discovery that activating and inactivating mutations in low-density lipoprotein receptor-related protein 5, a putative Wnt coreceptor, led to high bone mass and low bone mass in human beings, respectively, generated a tremendous amount of interest in the possible role of the Wnt signaling pathway in the regulation of bone remodeling. A number of mouse models have been generated to study a collection of Wnt signaling molecules that have been identified as regulators of bone mass. These mouse models help establish the canonical Wnt signaling pathway as a major regulator of chondrogenesis, osteoblastogenesis, and osteoclastogenesis. This review will summarize these advances.
Glass
Donald A
DA
Medical Scientist Training Prtogram, Baylor College of Medicine, Houston, TX 77030, USA.
Karsenty
Gerard
G
D000818:Animals; D001842:Bone and Bones / Q000502:physiology*; D038362:Glycogen Synthase Kinase 3 / Q000502:physiology; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins / Q000502:physiology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D047908:Intracellular Signaling Peptides and Proteins; D026502:LDL-Receptor Related Proteins / Q000502:physiology; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D060488:Low Density Lipoprotein Receptor-Related Protein-6; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D011973:Receptors, LDL / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D051820:TCF Transcription Factors / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000502:physiology; D000099274:Frizzled-Related Proteins
D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular 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; D011973:Receptors, LDL; D051820:TCF Transcription Factors; D051153:Wnt Proteins; D051176:beta Catenin; D000099274:Frizzled-Related Proteins; C501127:Dkk1 protein, mouse; C405060:Dkk2 protein, mouse; C555482:LRP5 protein, human; C555475:LRP6 protein, human; C555483:Lrp5 protein, mouse; C555476:Lrp6 protein, mouse