Inhibition of gut-derived serotonin synthesis: a potential bone anabolic treatment
| Autor: | Michael D. Gershon, Marc Vidal, S. Balaji, Anil K. Balapure, Patricia Ducy, Vijay K. Yadav, Gerard Karsenty, Rudraiah Medhamurthy, Zhishan Li, X. Sherry Liu, J. John Mann, X. Edward Guo, Padmanaban S. Suresh, Xin Lu |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: |
Serotonin
medicine.medical_specialty Anabolism Osteoporosis Tryptophan Hydroxylase Pharmacology Biology General Biochemistry Genetics and Molecular Biology Bone resorption Article Mice chemistry.chemical_compound Serotonin Agents Biosynthesis Osteogenesis Oral administration Internal medicine medicine Animals Humans Osteoporosis Postmenopausal Dose-Response Relationship Drug Tryptophan General Medicine medicine.disease Rats Gastrointestinal Tract Mice Inbred C57BL Pyrimidines Endocrinology chemistry Ovariectomized rat Female |
| Zdroj: | Nature medicine |
| ISSN: | 1546-170X 1078-8956 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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