Efficacy of serotonin inhibition in mouse models of bone loss

Journal of Bone and Mineral Research

Volumn 26, Issue 9, 2011, Pages 2002-2011

  Inose, Hiroyuki ^a   Zhou, Bin ^b   Yadav, Vijay K ^a,c   Guo, X Edward ^b   Karsenty, Gerard ^a   Ducy, Patricia ^a  

^a Department of Medicine   (United States)

^b Department of Earth and Environmental Sciences   (United States)

^c WELLCOME TRUST SANGER INSTITUTE   (United Kingdom)

Author keywords

ANABOLIC TREATMENT; BONE FORMATION; OSTEOPOROSIS; SEROTONIN; TPH1 INHIBITOR

Indexed keywords

ALENDRONIC ACID; CALCIUM; CARBOXY TERMINAL TELOPEPTIDE; COLECALCIFEROL; CYCLIN D1; CYCLIN D2; CYCLIN E; CYCLIN E1; LOW DENSITY LIPOPROTEIN RECEPTOR RELATED PROTEIN 5; LP 533401; OXYGENASE INHIBITOR; PHOSPHATE; SEROTONIN; SEROTONIN ANTAGONIST; TRYPTOPHAN HYDROXYLASE; UNCLASSIFIED DRUG;

AGED; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BONE ATROPHY; BONE MASS; CONTROLLED STUDY; DRUG DOSE COMPARISON; DRUG EFFECT; DRUG EFFICACY; DRUG POTENTIATION; ENZYME INHIBITION; FEMALE; LOW DRUG DOSE; MOUSE; NONHUMAN; OSSIFICATION; OSTEOPENIA; OSTEOPOROSIS; OVARIECTOMY; PHENOTYPE; PROTEIN BLOOD LEVEL; SEROTONIN BLOOD LEVEL; TREATMENT DURATION;

AGING; ALENDRONATE; ANIMALS; BONE AND BONES; BONE RESORPTION; DISEASE MODELS, ANIMAL; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG THERAPY, COMBINATION; FEMALE; GASTROINTESTINAL TRACT; LOW DENSITY LIPOPROTEIN RECEPTOR-RELATED PROTEIN-5; MICE; MICE, INBRED C57BL; ORGAN SIZE; OSTEOPOROSIS; OVARIECTOMY; PHENOTYPE; PYRIMIDINES; SEROTONIN; TIME FACTORS; TREATMENT OUTCOME; TRYPTOPHAN HYDROXYLASE;

EID: 80051989900     PISSN: 08840431     EISSN: 15234681     Source Type: Journal    
DOI: 10.1002/jbmr.439     Document Type: Article

References (31)

1. Yadav VK, Arantes HP, Barros ER, Lazaretti-Castro M, Ducy P,. Genetic analysis of Lrp5 function in osteoblast progenitors. Calcif Tissue Int. 2010; 86: 382-388.
2. Yadav VK, Ryu JH, Suda N, et al. Lrp5 controls bone formation by inhibiting serotonin synthesis in the duodenum. Cell. 2008; 135: 825-837.
3. Saarinen A, Saukkonen T, Kivela T, et al. LDL receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia. Clin Endocrinol (Oxf). 2009; 72: 481-488.
4. Frost M, Andersen TE, Yadav VK, Brixen K, Karsenty G, Kassem M,. Patients with high bone mass phenotype due to Lrp5-T253I mutation have low plasma levels of serotonin. J Bone Min Res. 2010; 25: 673-675.
5. Yadav VK, Balaji S, Suresh PS, et al. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med. 2010; 16: 308-312.
6. Gershon MD, Tack J,. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology. 2007; 132: 397-414. (Pubitemid 46127672)
7. Liu Q, Yang Q, Sun W, et al. Discovery and characterization of novel tryptophan hydroxylase inhibitors that selectively inhibit serotonin synthesis in the gastrointestinal tract. J Pharmacol Exp Ther. 2008; 325: 47-55. (Pubitemid 351439163)
8. Shi ZC, Devasagayaraj A, Gu K, et al. Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders. J Med Chem. 2008; 51: 3684-3687. (Pubitemid 351956498)
9. Kato M, Patel MS, Levasseur R, et al. Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor. J Cell Biol. 2002; 157: 303-314. (Pubitemid 34839826)
10. Vignery A, Baron R,. Dynamic histomorphometry of alveolar bone remodeling in the adult rat. Anat Rec. 1980; 196: 191-200. (Pubitemid 10155469)
11. Parfitt AM, Drezner MK, Glorieux FH, et al. Bone histomorphometry: standardization of nomenclature, symbols, and units. Report of the ASBMR Histomorphometry Committee. J Bone Miner Res. 1987; 6: 595-610.
12. Feldkamp LA, Goldstein SA, Parfitt AM, Jesion G, Kleerekoper M,. The direct examination of three-dimensional bone architecture in vitro by computed tomography. J Bone Miner Res. 1989; 4: 3-11. (Pubitemid 19079118)
13. Gundersen HJ, Boyce RW, Nyengaard JR, Odgaard A,. The Conneulor: unbiased estimation of connectivity using physical disectors under projection. Bone. 1993; 14: 217-222. (Pubitemid 23175732)
14. Clement-Lacroix P, Ai M, Morvan F, et al. Lrp5-independent activation of Wnt signaling by lithium chloride increases bone formation and bone mass in mice. Proc Natl Acad Sci U S A. 2005; 102: 17406-17411. (Pubitemid 41740879)
15. Otero Losada ME, Rubio MC,. Effects of i.c.v. lithium chloride administration on monoamine concentration in rat mediobasal hypothalamus. Eur J Pharmacol. 1992; 215: 185-189.
16. Scheuch K, Holtje M, Budde H, et al. Lithium modulates tryptophan hydroxylase 2 gene expression and serotonin release in primary cultures of serotonergic raphe neurons. Brain Res. 2010; 1307: 14-21.
17. Li J, Khavandgar Z, Lin SH, Murshed M,. Lithium chloride attenuates BMP-2 signaling and inhibits osteogenic differentiation through a novel WNT/GSK3- independent mechanism. Bone. 2011; 48: 321-331.
18. Khosla S, Riggs BL,. Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin North Am. 2005; 34: 1015-1030 xi. (Pubitemid 41677410)
19. Becker DJ, Kilgore ML, Morrisey MA,. The societal burden of osteoporosis. Curr Rheumatol Rep. 2010; 12: 186-191.
20. Deal C,. Future therapeutic targets in osteoporosis. Curr Opin Rheumatol. 2009; 21: 380-385.
21. Kawai M, Modder UI, Khosla S, Rosen CJ,. Emerging therapeutic opportunities for skeletal restoration. Nat Rev Drug Discov. 2011; 10: 141-156.
22. Khosla S,. Increasing options for the treatment of osteoporosis. N Engl J Med. 2009; 361: 818-820.
23. Gong Y, Slee RB, Fukai N, et al. LDL Receptor-Related Protein 5 (LRP5) Affects Bone Accrual and Eye Development. Cell. 2001; 107: 513-523. (Pubitemid 33152786)
24. Yadav VK, Oury F, Suda N, et al. A serotonin-dependent mechanism explains the leptin regulation of bone mass, appetite, and energy expenditure. Cell. 2009; 138: 976-989.
25. Lane NE, Silverman SL,. Anabolic therapies. Curr Osteoporos Rep. 2010; 8: 23-27.
26. Khosla S,. Parathyroid hormone plus alendronate - a combination that does not add up. N Engl J Med. 2003; 349: 1277-1279. (Pubitemid 37152038)
27. Girotra M, Rubin MR, Bilezikian JP,. The use of parathyroid hormone in the treatment of osteoporosis. Rev Endocr Metab Disord. 2006; 7: 113-121. (Pubitemid 46049523)
28. Black DM, Greenspan SL, Ensrud KE, et al. The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis. N Engl J Med. 2003; 349: 1207-1215. (Pubitemid 37152030)
29. Cosman F, Nieves J, Zion M, Woelfert L, Luckey M, Lindsay R,. Daily and cyclic parathyroid hormone in women receiving alendronate. N Engl J Med. 2005; 353: 566-575. (Pubitemid 41138938)
30. Zambrowicz B, Brown P, Jackson JI, et al. 2010. Serotonin biomaker levels correlate with clinical response in Phase 2 trial of LX1031, a novel serotonin synthesis inhibitor for non-constipating IBS Digestive Disease Week Meeting, New Orleans, LA.
31. Reagan-Shaw S, Nihal M, Ahmad N,. Dose translation from animal to human studies revisited. FASEB J. 2008; 22: 659-661. (Pubitemid 351348146)