Wnt signaling and osteoblastogenesis.

Abstract

Wnts are a large family of growth factors that mediate fundamental biological processes like embryogenesis, organogenesis and tumorigenesis. These proteins bind to a membrane receptor complex comprised of a frizzled (FZD) G-protein-coupled receptor (GPCRs) and a low-density lipoprotein (LDL) receptor-related protein (LRP). The formation of this ligand-receptor complex initiates a number of intracellular signaling cascades that includes the canonical/beta-catenin pathway, as well as several GPCR-mediated noncanonical pathways. In recent years, canonical Wnt signaling has been shown to play a substantial role in the control of bone formation. Clinical investigations have found that mutations in LRP-5 are associated with bone mineral density and fractures. For example, loss-of-function mutations in LRP-5 cause osteoporosis pseudoglioma syndrome, while gain-of-function mutations lead to high bone mass phenotypes. Studies of knockout and transgenic mouse models for Wnt pathway components like Wnt-10b, LRP-5/6, secreted frizzled-related protein-1, dickkopf-2, Axin-2 and beta-catenin have demonstrated that canonical signaling modulates most aspects of osteoblast physiology including proliferation, differentiation, bone matrix formation/mineralization and apoptosis as well as coupling to osteoclastogenesis and bone resorption. Future studies in this rapidly growing area of research should focus on elucidating Wnt/FZD specificity in the control of bone cell function, the role of noncanonical pathways in skeletal remodeling, and direct effects of Wnts on cells of the osteoclast lineage.

• Authors: Peter V N Bodine, Barry S Komm
• Journal: Reviews in endocrine & metabolic disorders (Rev Endocr Metab Disord) Vol. 7 Issue 1-2 Pg. 33-9 (Jun 2006) ISSN: 1389-9155 [Print] Germany
• PMID: 16960757 (Publication Type: Journal Article, Review)

Chemical References

• AXIN2 protein, human
• Axin Protein
• Cytoskeletal Proteins
• Dkk2 protein, mouse
• Intercellular Signaling Peptides and Proteins
• LDL-Receptor Related Proteins
• LRP5 protein, human
• LRP6 protein, human
• Low Density Lipoprotein Receptor-Related Protein-5
• Low Density Lipoprotein Receptor-Related Protein-6
• Lrp5 protein, mouse
• Lrp6 protein, mouse
• Membrane Proteins
• Receptors, LDL
• SFRP1 protein, human
• Wnt Proteins
• beta Catenin

Topics

• Animals
• Apoptosis (genetics)
• Axin Protein
• Calcification, Physiologic (genetics)
• Cell Differentiation (genetics)
• Cell Proliferation
• Cytoskeletal Proteins (physiology)
• Humans
• Intercellular Signaling Peptides and Proteins (physiology)
• LDL-Receptor Related Proteins (physiology)
• Low Density Lipoprotein Receptor-Related Protein-5
• Low Density Lipoprotein Receptor-Related Protein-6
• Membrane Proteins (physiology)
• Models, Biological
• Osteoblasts (cytology, physiology)
• Osteoclasts (cytology)
• Osteogenesis
• Receptors, LDL (physiology)
• Signal Transduction
• Wnt Proteins (genetics, physiology)
• beta Catenin (physiology)