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Cited by 834

The DOI matches its Crossref record; 8 of the 8 references it cites were found in a registry or an index.

Lrp5 Controls Bone Formation by Inhibiting Serotonin Synthesis in the Duodenum

Open access
Yadav, Vijay K., Ryu, Je-Hwang, Suda, Nina, Tanaka, Kenji F., Gingrich, Jay A., Schütz, Günther, Glorieux, Francis H., Chiang, Cherie Y., Zajac, Jeffrey D., Insogna, Karl L., Mann, J. John, Hen, Rene, Ducy, Patricia, Karsenty, Gerard·2008·Cell
DOI 10.1016/j.cell.2008.09.059
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Abstract

Loss- and gain-of-function mutations in the broadly expressed gene Lrp5 affect bone formation causing osteoporosis and high bone mass, respectively. Although Lrp5 is viewed as a Wnt coreceptor osteoblast-specific disruption of β-Catenin does not affect bone formation. Instead, we show here that Lrp5 inhibits expression of Tph1, the rate-limiting biosynthetic enzyme for serotonin in enterochromaffin cells of the duodenum. Accordingly, decreasing serotonin blood levels normalizes bone formation and bone mass in Lrp5-deficient mice and gut- but not osteoblast-specific Lrp5 inactivation decreases bone formation in a β-Catenin–independent manner. Moreover, gut-specific activation of Lrp5, or inactivation of Tph1, increases bone mass and prevents ovariectomy-induced bone loss. Serotonin acts on osteoblasts through the Htr1b receptor and CREB to inhibit their proliferation. By identifying duodenum-derived serotonin as a hormone inhibiting bone formation in an Lrp5-dependent manner this study broadens our understanding of bone remodeling and suggests novel therapies to increase bone mass.

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Metadata

Authors
Yadav, V. K., Ryu, J.-H., Suda, N., Tanaka, K. F., Gingrich, J. A., Schütz, G., Glorieux, F. H., Chiang, C. Y., Zajac, J. D., Insogna, K. L., Mann, J. J., Hen, R., Ducy, P., & Karsenty, G.
Venue
Cell
Publisher
Elsevier BV
Published
2008-11
Volume
135
Issue
5
Pages
825-837
ISSN
0092-8674 (ISSN-L)
DOI
10.1016/j.cell.2008.09.059
OpenAlex
W2073052871
Cited by
834
References
8
FWCI
31.64
Type
journal article
Language
en
Open access
bronze

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