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 Vol. 107; no. 4; pp. 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:	Journal Article
Language:	English
Published:	United States Elsevier Inc 16-11-2001 Elsevier
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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0092-8674 1097-4172
DOI:	10.1016/S0092-8674(01)00571-2