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Genetic Analysis of Lrp5 Function in Osteoblast Progenitors

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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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Acknowledgements

We thank M.-T. Rached and N. Suda for help with experiments. These studies were supported by grants from the NIH (V. K. Y. and P. D.) and a Gideon and Sevgi Rodan fellowship from IBMS (V. K. Y.).

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Authors and Affiliations

  1. Department of Genetics and Development, Columbia University Medical Center, New York, NY, 10032, USA

    Vijay K. Yadav

  2. Division of Endocrinology, São Paulo Federal University, Rua Pedro de Toledo, São Paulo, SP, 04039-032, Brazil

    Henrique Pierotti Arantes & Elizabete Ribeiro Barros

  3. Bone and Mineral Unit, São Paulo Federal University, Rua Pedro de Toledo, São Paulo, SP, 04039-032, Brazil

    Marise Lazaretti-Castro

  4. Department of Pathology, Columbia University Medical Center, New York, NY, 10032, USA

    Patricia Ducy

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  1. Vijay K. Yadav
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  2. Henrique Pierotti Arantes
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  3. Elizabete Ribeiro Barros
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  4. Marise Lazaretti-Castro
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Correspondence to Patricia Ducy.

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The authors declare no conflict of interests.

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Yadav, V.K., Arantes, H.P., Barros, E.R. et al. Genetic Analysis of Lrp5 Function in Osteoblast Progenitors. Calcif Tissue Int 86, 382–388 (2010). https://doi.org/10.1007/s00223-010-9350-7

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  • DOI: https://doi.org/10.1007/s00223-010-9350-7

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