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 language | English (US) |
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Pages (from-to) | 4-12 |
Number of pages | 9 |
Journal | Bone |
Volume | 46 |
Issue number | 1 |
DOIs | |
State | Published - Jan 2010 |
Keywords
- Antidepressants
- Enterochromaffin cells
- Hormones
- Osteoporosis
- Serotonin
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Physiology
- Histology