LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development

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.

Affiliations

¹The Osteoporosis-Pseudoglioma Syndrome Collaborative Group

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.

Links

DOI: 10.1016/S0092-8674(01)00571-2

PubMed: 11719191

WoS: 000172272900011

History

Received: 2001-04-2

Revised: 2001-11-16

Online: 2001-11-27

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