Genetic Analysis of Lrp5 Function in Osteoblast Progenitors |
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Authors: | Vijay K Yadav Henrique Pierotti Arantes Elizabete Ribeiro Barros Marise Lazaretti-Castro Patricia Ducy |
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Institution: | 1. Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA 2. Division of Endocrinology, S?o Paulo Federal University, Rua Pedro de Toledo, S?o Paulo, SP, 04039-032, Brazil 3. Bone and Mineral Unit, S?o Paulo Federal University, Rua Pedro de Toledo, S?o Paulo, SP, 04039-032, Brazil 4. Department of Pathology, Columbia University Medical Center, New York, NY, 10032, USA
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Abstract: | 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. |
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Keywords: | |
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