title: LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development.
abstract: 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.
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mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000818:Animals; D021461:Animals, Outbred Strains; D015519:Bone Density / Q000235:genetics*; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D019556:COS Cells; D002648:Child; D002675:Child, Preschool; D002522:Chlorocebus aethiops; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D017077:Culture Media, Conditioned / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D000072261:Dishevelled Proteins; D005123:Eye / Q000196:embryology*; D005124:Eye Abnormalities / Q000235:genetics*; D005260:Female; D005808:Genes, Recessive; D006579:Heterozygote; D006801:Humans; D026502:LDL-Receptor Related Proteins; D060492:Low Density Lipoprotein Receptor-Related Protein-5; D008297:Male; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques; D010006:Osteoblasts / Q000378:metabolism*; D010024:Osteoporosis / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011994:Recombinant Proteins; D015398:Signal Transduction; D012886:Skull / Q000166:cytology; D013045:Species Specificity; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects; D013577:Syndrome; D014162:Transfection; D016212:Transforming Growth Factor beta; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060528:Wnt4 Protein; D029961:Zebrafish Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C525718:BMP2 protein, human; C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D000072261:Dishevelled Proteins; D026502:LDL-Receptor Related Proteins; C555482:LRP5 protein, human; D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D010750:Phosphoproteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011973:Receptors, LDL; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C555581:WNT4 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D060508:Wnt3 Protein; D060528:Wnt4 Protein; C555582:Wnt4 protein, mouse; D029961:Zebrafish Proteins; C499469:recombinant human bone morphogenetic protein-2