The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5)

Stuart J. Warden, Alexander G. Robling, Elizabeth Haney, Charles H. Turner, Michael M. Bliziotes

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Novel molecular pathways obligatory for bone health are being rapidly identified. One pathway recently revealed involves gut-derived 5-hydroxytryptamine (5-HT) mediation of the complete skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). Mounting evidence supports 5-HT as an important regulatory compound in bone with previous evidence demonstrating that bone cells possess functional pathways for responding to 5-HT. In addition, there is growing evidence that potentiation of 5-HT signaling via inhibition of the 5-HT transporter (5-HTT) has significant skeletal effects. The later is clinically significant as the 5-HTT is a popular target of pharmaceutical agents, such as selective serotonin reuptake inhibitors (SSRIs), used for the management of major depressive disorder and other affective conditions. The observation that 5-HT mediates the complete skeletal effects of LRP5 represents a significant paradigm shift from the traditional view that LRP5 located on the cell surface membrane of osteoblasts exerts direct skeletal effects via Wnt/beta-catenin signaling. This paper discusses the mounting evidence for skeletal effects of 5-HT and the ability of gut-derived 5-HT to satisfactorily explain the skeletal effects of LRP5.

Original languageEnglish (US)
Pages (from-to)4-12
Number of pages9
JournalBone
Volume46
Issue number1
DOIs
StatePublished - Jan 2010

Fingerprint

Low Density Lipoprotein Receptor-Related Protein-5
Skeleton
Serotonin
Bone and Bones
Aptitude
Major Depressive Disorder
Serotonin Uptake Inhibitors
beta Catenin
Osteoblasts

Keywords

  • Antidepressants
  • Enterochromaffin cells
  • Hormones
  • Osteoporosis
  • Serotonin

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

The emerging role of serotonin (5-hydroxytryptamine) in the skeleton and its mediation of the skeletal effects of low-density lipoprotein receptor-related protein 5 (LRP5). / Warden, Stuart J.; Robling, Alexander G.; Haney, Elizabeth; Turner, Charles H.; Bliziotes, Michael M.

In: Bone, Vol. 46, No. 1, 01.2010, p. 4-12.

Research output: Contribution to journalArticle

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