Author/Authors :
Yaoqin Gong، نويسنده , , Roger B. Slee، نويسنده , , Naomi Fukai، نويسنده , , Georges Rawadi، نويسنده , , Sergio Roman-Roman، نويسنده , , Anthony M. Reginato، نويسنده , , Hongwei Wang، نويسنده , , Tim Cundy، نويسنده , , Francis H. Glorieux، نويسنده , , Dorit Lev، نويسنده , , Margaret Zacharin، نويسنده , , Konrad Oexle، نويسنده , , Jose Marcelino Oliveira Cavalheiro، نويسنده , , Wafaa Suwairi، نويسنده , , Shauna Heeger، نويسنده , , George Sabatakos، نويسنده , , Suneel Apte، نويسنده , , William N. Adkins، نويسنده , , Jeremy Allgrove، نويسنده , , Mine Arslan-Kirchner، نويسنده , , et al.، نويسنده ,
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.
