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 (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.
Gong, Y; Slee, RB; Fukai, N; Rawadi, G; Roman-Roman, S; Reginato, AM; Wang, H; Cundy, T; Glorieux, FH; Lev, D; Zacharin, M; Oexle, K; Marcelino, J; Suwairi, W; Heeger, S; Sabatakos, G; Apte, S; Adkins, WN; Allgrove, J; Arslan-Kirchner, M; Batch, JA; Beighton, P; Black, GC; Boles, RG; Boon, LM; Borrone, C; Brunner, HG; Carle, GF; Dallapiccola, B; De Paepe, A; Floege, B; Halfhide, ML; Hall, B; Hennekam, RC; Hirose, T; Jans, A; Jüppner, H; Kim, CA; Keppler-Noreuil, K; Kohlschuetter, A; LaCombe, D; Lambert, M; Lemyre, E; Letteboer, T; Peltonen, L; Ramesar, RS; Romanengo, M; Somer, H; Steichen-Gersdorf, E; Steinmann, B; Sullivan, B; Superti-Furga, A; Swoboda, W; van den Boogaard, MJ; Van Hul, W; Vikkula, M; Votruba, M; Zabel, B; Garcia, T; Baron, R; Olsen, BR; Warman, ML; Osteoporosis-Pseudoglioma Syndrome Collaborative Group,
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