Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis

Yadav, Vijay K and Balaji, Santhanam and Suresh, Padmanaban S and Liu, X Sherry and Lu, Xin and Li, Zhishan and Guo, X Edward and Mann, J John and Balapure, Anil K and Gershon, Michael D and Medhamurthy, Rudraiah and Vidal, Marc and Karsenty, Gerard and Ducy, Patricia (2010) Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. In: Nature Medicine, 16 (3). 308-U103.

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Abstract

Osteoporosis is a disease of low bone mass most often caused by an increase in bone resorption that is not sufficiently compensated for by a corresponding increase in bone formation(1). As gut-derived serotonin (GDS) inhibits bone formation(2), we asked whether hampering its biosynthesis could treat osteoporosis through an anabolic mechanism (that is, by increasing bone formation). We synthesized and used LP533401, a small molecule inhibitor of tryptophan hydroxylase-1 (Tph-1), the initial enzyme in GDS biosynthesis. Oral administration of this small molecule once daily for up to six weeks acts prophylactically or therapeutically, in a dose-dependent manner, to treat osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. These results provide a proof of principle that inhibiting GDS biosynthesis could become a new anabolic treatment for osteoporosis.

Item Type:	Journal Article
Publication:	Nature Medicine
Publisher:	Nature Publishing Group.
Additional Information:	Copyright of this article belongs to Nature Publishing Group.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Date Deposited:	23 Mar 2010 12:10
Last Modified:	16 Jan 2013 11:45
URI:	http://eprints.iisc.ac.in/id/eprint/26389

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