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-relate d protein 5, affects bone mass accrual during growth. Mutations in LRP5 cau se the autosomal recessive disorder osteoporosis-pseudoglioma syndrome (OPP G). 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 Writ signaling in vitro via the c anonical pathway. We further show that a mutant-secreted form of LRP5 can r educe bone thickness in mouse calvarial explant cultures. These data indica te that Wnt-mediated signaling via LRP5 affects bone accrual during growth and is important for the establishment of peak bone mass.