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- Title
Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis.
- Authors
Yadav, Vijay K; Balaji, Santhanam; Suresh, Padmanaban S; Liu, X Sherry; Lu, Xin; Li, Zhishan; Guo, X Edward; Mann, J John; Balapure, Anil K; Gershon, Michael D; Medhamurthy, Rudraiah; Vidal, Marc; Karsenty, Gerard; Ducy, Patricia
- 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. As gut-derived serotonin (GDS) inhibits bone formation, 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.
- Publication
Nature medicine, 2010, Vol 16, Issue 3, p308
- ISSN
1546-170X
- Publication type
Journal Article
- DOI
10.1038/nm.2098