Article: article from journal or magazin.
LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.
Osteoporosis-Pseudoglioma Syndrome Collaborative Group
In humans, low peak bone mass is a significant risk factor for osteoporosis. We report that LRP5, encoding the low-density lipoprotein receptor-related protein 5, affects bone mass accrual during growth. Mutations in LRP5 cause the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPPG). We find that OPPG carriers have reduced bone mass when compared to age- and gender-matched controls. We demonstrate LRP5 expression by osteoblasts in situ and show that LRP5 can transduce Wnt signaling in vitro via the canonical pathway. We further show that a mutant-secreted form of LRP5 can reduce bone thickness in mouse calvarial explant cultures. These data indicate that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.
Adaptor Proteins, Signal Transducing, Adult, Animals, Animals, Outbred Strains, Bone Density/genetics, Bone Morphogenetic Protein 2, Bone Morphogenetic Proteins/pharmacology, COS Cells, Cercopithecus aethiops, Child, Child, Preschool, Chromosomes, Human, Pair 11/genetics, Culture Media, Conditioned/pharmacology, DNA, Complementary/genetics, Eye/embryology, Eye Abnormalities/genetics, Female, Genes, Recessive, Heterozygote, Humans, LDL-Receptor Related Proteins, Male, Mesoderm/cytology, Mice, Mice, Inbred C57BL, Organ Culture Techniques, Osteoblasts/metabolism, Osteoporosis/genetics, Phosphoproteins/genetics, Phosphoproteins/physiology, Proteins/genetics, Proteins/physiology, Proto-Oncogene Proteins/genetics, Proto-Oncogene Proteins/physiology, Receptors, LDL/deficiency, Receptors, LDL/genetics, Recombinant Fusion Proteins/physiology, Recombinant Proteins, Signal Transduction, Skull/cytology, Species Specificity, Stromal Cells/cytology, Stromal Cells/drug effects, Syndrome, Transfection, Transforming Growth Factor beta, Wnt Proteins, Wnt2 Protein, Zebrafish Proteins
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