title: Serotonin: a novel bone mass controller may have implications for alveolar bone.
abstract: As recent studies highlight the importance of alternative mechanisms in the control of bone turnover, new therapeutic approaches can be envisaged for bone diseases and periodontitis-induced bone loss. Recently, it has been shown that Fluoxetine and Venlafaxine, serotonin re-uptake inhibitors commonly used as antidepressants, can positively or negatively affect bone loss in rat models of induced periodontitis. Serotonin is a neurotransmitter that can be found within specific nuclei of the central nervous system, but can also be produced in the gut and be sequestered inside platelet granules. Although it is known to be mainly involved in the control of mood, sleep, and intestinal physiology, recent evidence has pointed at far reaching effects on bone metabolism, as a mediator of the effects of Lrp5, a membrane receptor commonly associated with Wnt canonical signaling and osteoblast differentiation. Deletion of Lrp5 in mice lead to increased expression of Tryptophan Hydroxylase 1, the gut isoform of the enzyme required for serotonin synthesis, thus increasing serum levels of serotonin. Serotonin, in turn, could bind to HTR1B receptors on osteoblasts and stop their proliferation by activating PKA and CREB.Although different groups have reported controversial results on the existence of an Lrp5-serotonin axis and the action of serotonin in bone remodeling, there is convincing evidence that serotonin modulators such as SSRIs can affect bone turnover. Consequently, the effects of this drug family on periodontal physiology should be thoroughly explored.
authors: Dep, Biomedicine, Biotechnology and Translational Sciences, University of Parma, Via Gramsci 14, Parma 43126, Italy. guidomaria.macaluso@unipr.it.
authors: Carlo
authors: C
authors: Galli
authors: Guido
authors: G
authors: Macaluso
authors: Giovanni
authors: G
authors: Passeri
mesh_terms: D000539:Alveolar Process / Q000033:anatomy & histology* / Q000378:metabolism*; D000818:Animals; D060492:Low Density Lipoprotein Receptor-Related Protein-5 / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D009929:Organ Size; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D060492:Low Density Lipoprotein Receptor-Related Protein-5; C555483:Lrp5 protein, mouse; D012701:Serotonin
references: Cell. 2009 Sep 4;138(5):976-89
references: 19737523
references: Philos Trans R Soc Lond B Biol Sci. 2012 Sep 5;367(1601):2378-81
references: 22826338
references: J Cell Biol. 2002 Apr 15;157(2):303-14
references: 11956231
references: N Engl J Med. 2002 May 16;346(20):1513-21
references: 12015390
references: Eur J Pharmacol. 2012 Aug 5;688(1-3):42-8
references: 22546225
references: J Bone Miner Res. 2008 Oct;23(10):1661-71
references: 18505367
references: CNS Drugs. 2012 Jun 1;26(6):537-47
references: 22612695
references: Dev Biol. 2007 Jun 1;306(1):50-65
references: 17433285
references: Osteoporos Int. 2013 Jan;24(1):121-37
references: 22638709
references: J Clin Psychiatry. 2011 Dec;72(12):1685-90
references: 22244026
references: Cell. 2006 Nov 3;127(3):469-80
references: 17081971
references: J Biol Chem. 2006 Aug 11;281(32):22429-33
references: 16793760
references: Cell. 1997 Mar 21;88(6):725-8
references: 9118212
references: Nat Med. 2011 Sep 11;17(10):1235-41
references: 21909103
references: Nat Rev Mol Cell Biol. 2009 Apr;10(4):276-86
references: 19305417
references: Domest Anim Endocrinol. 2013 May;44(4):176-84
references: 23433710
references: Neurosci Lett. 2005 Feb 1;374(1):53-7
references: 15631896
references: Biol Psychiatry. 2013 Jul 1;74(1):32-9
references: 23260229
references: Pharmacol Ther. 2011 Jul;131(1):61-79
references: 21447358
references: Arthritis Res Ther. 2011 Apr 28;13(2):211
references: 21542893
references: Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L500-8
references: 22797248
references: Nat Rev Mol Cell Biol. 2009 Jul;10(7):468-77
references: 19536106
references: J Periodontol. 2012 May;83(5):664-71
references: 21966942
references: Nat Med. 2010 Mar;16(3):308-12
references: 20139991
references: Br J Pharmacol. 2004 Apr;141(8):1285-93
references: 15100164
references: Respir Res. 2007 May 03;8:35
references: 17477857
references: J Negat Results Biomed. 2010 Jun 14;9:3
references: 20546603
references: J Cell Biochem. 2006 Apr 15;97(6):1283-91
references: 16329113
references: Development. 2006 Aug;133(16):3231-44
references: 16854976
references: Eur Arch Psychiatry Clin Neurosci. 2013 Mar;263(2):105-18
references: 22752684
references: Nat Med. 2011 Jun;17(6):684-91
references: 21602802
references: Calcif Tissue Int. 2010 May;86(5):382-8
references: 20333369
references: Early Hum Dev. 2012 Mar;88(3):191-4
references: 21890289
references: Acta Reumatol Port. 2011 Jan-Mar;36(1):14-9
references: 21483275
references: Bone. 2011 Nov;49(5):1010-9
references: 21855668
references: J Clin Invest. 2006 May;116(5):1202-9
references: 16670761
references: Nat Med. 2009 Jul;15(7):757-65
references: 19584867
references: Mol Biol Cell. 2011 Jun 1;22(11):1845-63
references: 21471006
references: J Cell Biochem. 2006 May 1;98(1):139-51
references: 16408289
references: J Bone Miner Res. 2011 Sep;26(9):2002-11
references: 21608033
references: J Adolesc Health. 2012 Aug;51(2 Suppl):S9-16
references: 22794534
references: J Psychiatry Neurosci. 2012 Jan;37(1):7-16
references: 21711983
references: J Bone Miner Res. 2010 Mar;25(3):673-5
references: 20200960
references: Dev Dyn. 2010 Jan;239(1):34-44
references: 19623618
references: Curr Biol. 1996 Oct 1;6(10):1302-6
references: 8939578
references: Cell. 2008 Nov 28;135(5):825-37
references: 19041748
references: Sci Signal. 2008 Sep 02;1(35):re9
references: 18765832
references: Dev Cell. 2005 May;8(5):751-64
references: 15866165
references: Pharmacol Biochem Behav. 2002 Apr;71(4):533-54
references: 11888546
references: J Biol Chem. 2009 May 8;284(19):12654-62
references: 19279010
references: Drugs Aging. 2011 May 1;28(5):345-67
references: 21542658
references: Osteoporos Int. 2012 Jan;23(1):365-75
references: 21904950
references: J Bone Miner Res. 2011 Sep;26(9):1997-2001
references: 21713997
references: Cell. 2001 Nov 16;107(4):513-23
references: 11719191
references: J Chem Neuroanat. 2012 Mar;43(2):96-102
references: 22285725
references: Ann Med. 1990;22(5):327-31
references: 2291840
references: Age Ageing. 2013 Jul;42(4):514-20
references: 23438446
references: J Cell Biochem. 2007 May 15;101(2):360-8
references: 17163489
references: Synapse. 2008 Aug;62(8):590-600
references: 18509851
references: Nat Neurosci. 2008 Apr;11(4):417-9
references: 18344997
references: J Osteoporos. 2012;2012:323061
references: 22496984
references: Clin Endocrinol (Oxf). 2010 Apr;72(4):481-8
references: 19673927
references: J Oral Sci. 2008 Jun;50(2):193-8
references: 18587210
references: J Bone Miner Res. 2012 May;27(5):1186-95
references: 22258738
references: Osteoporos Int. 2013 May;24(5):1741-9
references: 23358607
references: Crit Rev Eukaryot Gene Expr. 2011;21(3):207-36
references: 22111711
references: Eur J Pharmacol. 2000 Dec 27;410(2-3):165-181
references: 11134668
references: Blood. 2012 Apr 12;119(15):3394-402
references: 22337717
references: Brain. 2012 Aug;135(Pt 8):2375-89
references: 22798270