5-HT and bone biology

Current Opinion in Pharmacology

Volumn 11, Issue 1, 2011, Pages 34-38

  Ducy, Patricia ^a  

^a New York Presbyterian Morgan Stanley Children's Hospital   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH FACTOR; HORMONE; LP 533401; SEROTONIN; SEROTONIN 1B ANTAGONIST; SEROTONIN 1B RECEPTOR; SEROTONIN 2C AGONIST; SEROTONIN 2C RECEPTOR; SEROTONIN UPTAKE INHIBITOR; TRYPTOPHAN HYDROXYLASE; TRYPTOPHAN HYDROXYLASE 1; TRYPTOPHAN HYDROXYLASE 2; UNCLASSIFIED DRUG;

ARTICLE; BONE MASS; BRAIN; CELL TYPE; DRUG TARGETING; GENE; HUMAN; INTESTINE; NONHUMAN; OSSIFICATION; OSTEOLYSIS; PRIORITY JOURNAL; REGULATORY MECHANISM; TPH1 GENE; TPH2 GENE;

EID: 79953694768     PISSN: 14714892     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.coph.2011.01.007     Document Type: Review

References (36)

1. G. Karsenty Convergence between bone and energy homeostases: leptin regulation of bone mass Cell Metab 4 2006 341 348 (Pubitemid 44645074)
2. J. Wei, and P. Ducy Co-dependence of bone and energy metabolisms Arch Biochem Biophys 503 2010 35 40
3. W. Balemans, and W. Van Hul The genetics of low-density lipoprotein receptor-related protein 5 in bone: a story of extremes Endocrinology 148 2007 2622 2629 (Pubitemid 46984773)
4. L.M. Boyden, J. Mao, J. Belsky, L. Mitzner, A. Farhi, M.A. Mitnick, D. Wu, K. Insogna, and R.P. Lifton High bone density due to a mutation in LDL-receptor-related protein 5 N Engl J Med 346 2002 1513 1521 (Pubitemid 34755690)
5. Y. Gong, R.B. Slee, N. Fukai, G. Rawadi, S. Roman-Roman, A.M. Reginato, H. Wang, T. Cundy, F.H. Glorieux, and D. Lev LDL receptor-related protein 5 (LRP5) affects bone accrual and eye development Cell 107 2001 513 523 (Pubitemid 33152786)
6. M. Kato, M.S. Patel, R. Levasseur, I. Lobov, B.H. Chang, D.A. Glass 2nd, C. Hartmann, L. Li, T.H. Hwang, and C.F. Brayton Cbfa1-independent decrease in osteoblast proliferation, osteopenia, and persistent embryonic eye vascularization in mice deficient in Lrp5, a Wnt coreceptor J Cell Biol 157 2002 303 314 (Pubitemid 34839826)
7. 1B these authors demonstrate that gut-derived 5-HT is an inhibitor of osteoblast proliferation whose increased blood level causes the bone loss associated with Osteoporosis Pseudoglioma in patients and Lrp5-deficiency in mice. This is the frst study showing that Lrp5 acts on bone mass by regulating Tph1 expression in gut.
8. V.K. Yadav, H.P. Arantes, E.R. Barros, M. Lazaretti-Castro, and P. Ducy Genetic analysis of Lrp5 function in osteoblast progenitors Calcif Tissue Int 86 2010 382 388
9. M. Frost, T.E. Andersen, V.K. Yadav, K. Brixen, G. Karsenty, and M. Kassem Patients with high bone mass phenotype due to Lrp5-T253I mutation have low plasma levels of serotonin J Bone Miner Res 25 2010 673 675 This manuscript reports that patients with the High bone mass syndrome, which is caused by activating mutations in the Lrp5 gene, have lower levels of blood serotonin.
10. A. Saarinen, T. Saukkonen, T. Kivela, U. Lahtinen, C. Laine, M. Somer, S. Toiviainen-Salo, W.G. Cole, A.E. Lehesjoki, and O. Makitie LDL receptor-related protein 5 (LRP5) mutations and osteoporosis, impaired glucose metabolism and hypercholesterolaemia Clin Endocrinol (Oxf) 72 2010 481 488
11. V.K. Yadav, and P. Ducy Lrp5 and bone formation: a serotonin-dependent pathway Ann N Y Acad Sci 1192 2010 103 109
12. H.G. Hanley, S.M. Stahl, and D.X. Freedman Hyperserotonemia and amine metabolites in autistic and retarded children Arch Gen Psychiatry 34 1977 521 531 (Pubitemid 8108951)
13. M.L. Hediger, L.J. England, C.A. Molloy, K.F. Yu, P. Manning-Courtney, and J.L. Mills Reduced bone cortical thickness in boys with autism or autism spectrum disorder J Autism Dev Disord 38 2008 848 856 (Pubitemid 351601312)
14. U.I. Modder, S.J. Achenbach, S. Amin, B.L. Riggs, L.J. Melton 3rd, and S. Khosla Relation of serum serotonin levels to bone density and structural parameters in women J Bone Miner Res 25 2010 415 422
15. P. Ducy, M. Amling, S. Takeda, M. Priemel, A.F. Schilling, F.T. Beil, J. Shen, C. Vinson, J.M. Rueger, and G. Karsenty Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass Cell 100 2000 197 207 (Pubitemid 30064908)
16. S. Takeda, F. Elefteriou, R. Levasseur, X. Liu, L. Zhao, K.L. Parker, D. Armstrong, P. Ducy, and G. Karsenty Leptin regulates bone formation via the sympathetic nervous system Cell 111 2002 305 317 (Pubitemid 35345151)
17. F. Elefteriou, J.D. Ahn, S. Takeda, M. Starbuck, X. Yang, X. Liu, H. Kondo, W.G. Richards, T.W. Bannon, and M. Noda Leptin regulation of bone resorption by the sympathetic nervous system and CART Nature 434 2005 514 520 (Pubitemid 40477060)
18. 2C as well as neuron tracing experiments to demonstrate that leptin mediates its central effects on bone mass accrual and appetite by inhibiting 5-HT synthesis in brainstem neurons. This paper also shows that mice deficient in both Tph1 and Tph2 have, as the Tph2-null mice have, a low bone mass phenotype caused by decreased bone formation and increased bone resorption.
19. A.W. Brotman, and T.A. Stern Osteoporosis and pathologic fractures in anorexia nervosa Am J Psychiatry 142 1985 495 496 (Pubitemid 15108218)
20. J. Oswiecimska, K. Ziora, W. Pluskiewicz, G. Geisler, K. Broll-Waska, D. Karasek, and A. Dyduch Skeletal status and laboratory investigations in adolescent girls with anorexia nervosa Bone 41 2007 103 110 (Pubitemid 46901059)
21. M. Stanley, L. Traskman-Bendz, and K. Dorovini-Zis Correlations between aminergic metabolites simultaneously obtained from human CSF and brain Life Sci 37 1985 1279 1286 (Pubitemid 15013197)
22. F. Oury, V.K. Yadav, Y. Wang, B. Zhou, X.S. Liu, X.E. Guo, L.H. Tecott, G. Schutz, A.R. Means, and G. Karsenty CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons Genes Dev 24 2010 2330 2342 This manuscript establishes that brain 5-HT causes its positive effect on bone mass accrual by activating the transcription factor CREB via a CaMK-dependent cascade in ventromedial hypothalamic neurons. Using a microarray strategy this study also identifies CREB target genes that mediates brain 5-HT inhibition of sympathetic output.
23. G.A. Rodan, and T.J. Martin Therapeutic approaches to bone diseases Science 289 2000 1508 1514
24. P.R. Ebeling, and R.G. Russell Teriparatide (rhPTH 1-34) for the treatment of osteoporosis Int J Clin Pract 57 2003 710 718 (Pubitemid 37428209)
25. F.E. Vegni, C. Corradini, and G. Privitera Effects of parathyroid hormone and alendronate alone or in combination in osteoporosis N Engl J Med 350 2004 189 192 author reply 189-192 (Pubitemid 38056234)
26. A.B. Hodsman, D.C. Bauer, D.W. Dempster, L. Dian, D.A. Hanley, S.T. Harris, D.L. Kendler, M.R. McClung, P.D. Miller, and W.P. Olszynski Parathyroid hormone and teriparatide for the treatment of osteoporosis: a review of the evidence and suggested guidelines for its use Endocr Rev 26 2005 688 703 (Pubitemid 41127277)
27. F. Saudou, D.A. Amara, A. Dierich, M. LeMeur, S. Ramboz, L. Segu, M.C. Buhot, and R. Hen Enhanced aggressive behavior in mice lacking 5-HT1B receptor Science 265 1994 1875 1878
28. M. Berger, J.A. Gray, and B.L. Roth The expanded biology of serotonin Annu Rev Med 60 2009 355 366
29. M. Filip, and M. Bader Overview on 5-HT receptors and their role in physiology and pathology of the central nervous system Pharmacol Rep 61 2009 761 777
30. S. Graham, D. Hammond-Jones, Z. Gamie, I. Polyzois, and E. Tsiridis The effect of beta-blockers on bone metabolism as potential drugs under investigation for osteoporosis and fracture healing Expert Opin Investig Drugs 17 2008 1281 1299
31. N. Bonnet, C. Gadois, E. McCloskey, G. Lemineur, E. Lespessailles, D. Courteix, and C.L. Benhamou Protective effect of beta blockers in postmenopausal women: influence on fractures, bone density, micro and macroarchitecture Bone 40 2007 1209 1216 (Pubitemid 46553796)
32. S.J. Warden, A.G. Robling, M.S. Sanders, M.M. Bliziotes, and C.H. Turner Inhibition of the serotonin (5-hydroxytryptamine) transporter reduces bone accrual during growth Endocrinology 146 2005 685 693 (Pubitemid 40129824)
33. E.M. Haney, B.K. Chan, S.J. Diem, K.E. Ensrud, J.A. Cauley, E. Barrett-Connor, E. Orwoll, and M.M. Bliziotes Association of low bone mineral density with selective serotonin reuptake inhibitor use by older men Arch Intern Med 167 2007 1246 1251 (Pubitemid 46998495)
34. S.J. Diem, T.L. Blackwell, K.L. Stone, K. Yaffe, E.M. Haney, M.M. Bliziotes, and K.E. Ensrud Use of antidepressants and rates of hip bone loss in older women: the study of osteoporotic fractures Arch Intern Med 167 2007 1240 1245 (Pubitemid 46998494)
35. Z.C. Shi, A. Devasagayaraj, K. Gu, H. Jin, B. Marinelli, L. Samala, S. Scott, T. Stouch, A. Tunoori, and Y. Wang Modulation of peripheral serotonin levels by novel tryptophan hydroxylase inhibitors for the potential treatment of functional gastrointestinal disorders J Med Chem 51 2008 3684 3687 (Pubitemid 351956498)
36. V.K. Yadav, S. Balaji, P.S. Suresh, X.S. Liu, X. Lu, Z. Li, X.E. Guo, J.J. Mann, A.K. Balapure, and M.D. Gershon Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis Nat Med 16 2010 308 312 This paper uses a compound able to inhibit 5-HT synthesis in gut but leaves brain 5-HT content unchanged to prevent or treat the bone loss caused by ovariectomy, a model of osteoporosis, in mice and rats. This is the first proof-of-concept study showing that specifically inhibiting 5-HT production in gut via a pharmacologic approach could become an anabolic treatment for osteoporosis.