LDL-receptor related protein five controls bone formation by inhibiting serotonin synthesis in the duodenum

Abstract

ABSTRACT LDL-receptor–related protein 5 (LRP5) is a widely expressed gene that plays a major regulatory role in bone formation. LRP5 loss-of-function mutations cause osteoporosis pseudoglioma, a rare bone disease characterized by severe decreased bone formation. Activating mutations in LRP5 stimulate bone formation and appear to be responsible for another bone disease, the high bone mass syndrome. Because it has been assumed that LRP5 is a co-receptor for Wnt proteins, the vertebrate homologs of the drosophila growth factor wingless osteoporosis pseudoglioma and high bone mass syndrome have been viewed as Wnt-related diseases. This view has been challenged in large part because osteoblast-sp..