LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development

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 (OPP...

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Published in:Cell 2001-11, Vol.107 (4), p.513-523
Main Authors: Gong, Yaoqin, Slee, Roger B., Fukai, Naomi, Rawadi, Georges, Roman-Roman, Sergio, Reginato, Anthony M., Wang, Hongwei, Cundy, Tim, Glorieux, Francis H., Lev, Dorit, Zacharin, Margaret, Oexle, Konrad, Marcelino, Jose, Suwairi, Wafaa, Heeger, Shauna, Sabatakos, George, Apte, Suneel, Adkins, William N., Allgrove, Jeremy, Arslan-Kirchner, Mine, Batch, Jennifer A., Beighton, Peter, Black, Graeme C.M., Boles, Richard G., Boon, Laurence M., Borrone, Carla, Brunner, Han G., Carle, Georges F., Dallapiccola, Bruno, De Paepe, Anne, Floege, Barbara, Halfhide, Melissa Lees, Hall, Bryan, Hennekam, Raoul C., Hirose, Tatsuo, Jans, Ab, Jüppner, Harald, Kim, Chong Ae, Keppler-Noreuil, Kim, Kohlschuetter, Alfried, LaCombe, Didier, Lambert, Marie, Lemyre, Emmanuelle, Letteboer, Tom, Peltonen, Leena, Ramesar, Rajkumar S., Romanengo, Marta, Somer, Hannu, Steichen-Gersdorf, Elisabeth, Steinmann, Beat, Sullivan, Beth, Superti-Furga, Andrea, Swoboda, Walter, van den Boogaard, Marie-José, Van Hul, Wim, Vikkula, Miikka, Votruba, Marcela, Zabel, Bernhard, Garcia, Teresa, Baron, Roland, Olsen, Bjorn R., Warman, Matthew L.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing
Adult
Animals
Animals, Outbred Strains
Biochemistry, Molecular Biology
Bone Density
Bone Density - genetics
Bone Morphogenetic Protein 2
Bone Morphogenetic Proteins
Bone Morphogenetic Proteins - pharmacology
Cercopithecus aethiops
Child
Child, Preschool
Chromosomes, Human, Pair 11
Chromosomes, Human, Pair 11 - genetics
COS Cells
Culture Media, Conditioned
Culture Media, Conditioned - pharmacology
Dishevelled Proteins
DNA, Complementary
DNA, Complementary - genetics
Eye
Eye - embryology
Eye Abnormalities
Eye Abnormalities - genetics
Female
Genes, Recessive
Heterozygote
Humans
LDL receptor-related protein 5
LDL-Receptor Related Proteins
Life Sciences
Low Density Lipoprotein Receptor-Related Protein-5
LRP5 protein
Male
Mesoderm
Mesoderm - cytology
Mice
Mice, Inbred C57BL
Organ Culture Techniques
Osteoblasts
Osteoblasts - metabolism
Osteoporosis
Osteoporosis - genetics
osteoporosis-pseudoglioma syndrome
Phosphoproteins
Phosphoproteins - genetics
Phosphoproteins - physiology
Proteins
Proteins - genetics
Proteins - physiology
Proto-Oncogene Proteins
Proto-Oncogene Proteins - genetics
Proto-Oncogene Proteins - physiology
Receptors, LDL
Receptors, LDL - deficiency
Receptors, LDL - genetics
Receptors, LDL - physiology
Recombinant Fusion Proteins
Recombinant Fusion Proteins - physiology
Recombinant Proteins
Signal Transduction
Skull
Skull - cytology
Species Specificity
Stromal Cells
Stromal Cells - cytology
Stromal Cells - drug effects
Syndrome
Transfection
Transforming Growth Factor beta
Wnt Proteins
Wnt-5a Protein
Wnt2 Protein
Wnt3 Protein
Wnt4 Protein
Zebrafish Proteins
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Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/S0092-8674(01)00571-2