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FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin
Aruna Kode1, Ioanna Mosialou, Barbara C Silva
1Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA.
The Journal of Clinical Investigation
|September 5, 2012
Summary
Duodenum-derived serotonin inhibits bone formation by altering the transcription factor FOXO1
Area of Science:
- Molecular biology
- Bone biology
- Endocrinology
Background:
- Serotonin regulates bone mass, with brain-derived serotonin promoting osteoblast proliferation.
- Duodenal-derived serotonin, however, suppresses osteoblast proliferation, indicating site-specific functions.
Purpose of the Study:
- To elucidate the molecular mechanisms by which duodenal-derived serotonin inhibits osteoblast proliferation.
- To identify the transcriptional mediators involved in this process in mice.
Main Methods:
- Investigated the role of transcription factors in mediating duodenal serotonin's effects on osteoblasts.
- Analyzed FOXO1 complex formation with CREB and ATF4 under varying serotonin levels in mice.
Main Results:
- FOXO1 is identified as a key transcription factor in duodenal serotonin's regulation of bone formation.
- FOXO1 forms complexes with CREB and ATF4 in osteoblasts.
- High circulating serotonin disrupts the FOXO1-CREB interaction, suppressing osteoblast proliferation.
Conclusions:
- FOXO1 acts as a molecular hub integrating signals for duodenal serotonin to inhibit bone formation.
- The balance of FOXO1 interactions with CREB and ATF4 is critical for regulating osteoblast proliferation under different serotonin levels.
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