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Lrp5 regulation of bone mass and serotonin synthesis in the gut

Nature Medicine volume 20, pages 1228–1229 (2014)Cite this article

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To the Editor:

We have proposed that the surface molecule Lrp5 favors bone formation by acting in enterochromaffin cells of the gut to inhibit the expression of Tph1, the initial enzyme in the serotonin synthetic pathway in these cells1. In support of this notion, different inhibitors of Tph1 activity can reverse osteoporosis in rodents2,3. In contrast, Cui et al. have proposed that Lrp5 favors bone formation in an osteoblast-autonomous manner4. To address this discrepancy, we studied the mice generated by Cui et al. and available from the Jackson Laboratory (Supplementary Methods).

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Figure 1: Changes in duodenal Tph1 expression and circulating serotonin in mouse models of Lrp5 loss and gain of function.

References

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Acknowledgements

We thank H. Liu for handling the mouse colony, A. Tarasenko for technical assistance and R. Axel for invaluable advice. We thank H. Jiang and S. Cremers of the Clinical and Translational Science Award Program at Columbia University Medical Center for measuring whole-blood serotonin content. This publication was supported by the National Center for Advancing Translational Sciences, US National Institutes of Health (NIH), through grant UL1 TR000040. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. This work was supported by NIH grant P01-AG032959.

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Author notes

  1. Aruna Kode, Arnaud Obri and Riccardo Paone: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiology & Cellular Biophysics, College of Physicians & Surgeons, Columbia University, New York, New York, USA

    Aruna Kode & Stavroula Kousteni

  2. Department of Genetics & Development, College of Physicians & Surgeons, Columbia University, New York, New York, USA

    Arnaud Obri & Gerard Karsenty

  3. Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy

    Riccardo Paone

  4. Department of Pathology & Cell Biology, College of Physicians & Surgeons, Columbia University, New York, New York, USA

    Patricia Ducy

Authors
  1. Aruna Kode
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  2. Arnaud Obri
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  3. Riccardo Paone
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  4. Stavroula Kousteni
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  5. Patricia Ducy
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  6. Gerard Karsenty
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Contributions

A.K., A.O. and R.P. performed the experiments and prepared the figures. S.K., P.D. and G.K. designed the study and wrote the paper.

Corresponding authors

Correspondence to Stavroula Kousteni, Patricia Ducy or Gerard Karsenty.

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The authors declare no competing financial interests.

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Kode, A., Obri, A., Paone, R. et al. Lrp5 regulation of bone mass and serotonin synthesis in the gut. Nat Med 20, 1228–1229 (2014). https://doi.org/10.1038/nm.3698

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