Genetic analysis of Lrp5 function in osteoblast progenitors.

The low-density lipoprotein receptor-related protein (Lrp)-5 regulates osteoblast proliferation and bone formation through its expression in duodenum by modifying the gut serotonin-bone endocrine axis. However, its direct role, if any, in osteoblast progenitor cells has not been studied thus far. Here, we show that mice with a Dermo1-Cre-mediated disruption of Lrp5 in osteoblast progenitor cells have normal embryonic skeletogenesis and normal skeletal growth and development postnatally. Histomorphometric analysis of 3-month-old adult mice revealed normal osteoblast numbers, bone formation rate, and bone mass in Lrp5(Dermo)(-/-) mice. In addition, analysis of two osteoporosis pseudoglioma (OPPG) patients revealed a three- to fivefold increase in their serum serotonin levels compared to age-matched controls. These results rule out a direct function of Lrp5 in osteoblast progenitor cells and add further support to the notion that dysregulation of serotonin synthesis is involved in bone mass abnormalities observed in OPPG patients.