ArticleThe Journal of clinical investigation2012
FOXO1 orchestrates the bone-suppressing function of gut-derived serotonin.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 76 citations in OpenAlex.
- Metabolomic biomarkers of low BMD: a systematic review.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Pooled it
- A barrier-centered perspective on the gut-barrier-bone axis: a review of the core role of the intestinal barrier and related probiotics with nanocoatings.Archives of microbiology · 2026Review
- Neuroendocrine and neural control of bone mass in health and disease.The Journal of clinical investigation · 2026Review
- Gut microbiota and bone aging: Focusing on the gut-X axis modes.Journal of orthopaedic translation · 2026Review
- Gut-bone axis: mechanisms and intervention effects of Chinese botanical drugs in osteoporosis management.Frontiers in pharmacology · 2026Review
- Periosteum Organoid: Biomimetic Design Inspired From the Bone Healing Process.Exploration (Beijing, China) · 2025Review
- Targeting the central and peripheral nervous system to regulate bone homeostasis: mechanisms and potential therapies.Military Medical Research · 2025Review
- Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges.Bone research · 2023Review
- Ring neurons in the Drosophila central complex act as a rheostat for sensory modulation of aging.PLoS biology · 2023Article
- The FOXO1 inhibitor AS1842856 triggers apoptosis in glioblastoma multiforme and basal-like breast cancer cells.FEBS open bio · 2023Article
- Article
- Exploring the mechanism of traditional Chinese medicine in regulating gut-derived 5-HT for osteoporosis treatment.Frontiers in endocrinology · 2023Review
- Antipsychotic-induced bone loss: the role of dopamine, serotonin and adrenergic receptor signalling.Frontiers in cell and developmental biology · 2023Review
- The Lignan-Rich Fraction fromNutrients · 2022Article
- CCND3 is indispensable for the maintenance of B-cell acute lymphoblastic leukemia.Oncogenesis · 2022Article
- Elucidating the Possible Role of FoxO in Depression.Neurochemical research · 2021Review
- The Mechanism of Secretion and Metabolism of Gut-Derived 5-Hydroxytryptamine.International journal of molecular sciences · 2021Review
- Milk and Dairy Products: Good or Bad for Human Bone? Practical Dietary Recommendations for the Prevention and Management of Osteoporosis.Nutrients · 2021Review
- PERK signaling pathway in bone metabolism: Friend or foe?Cell proliferation · 2021Review
- Depression and Antidepressants During Pregnancy: Craniofacial Defects Due to Stem/Progenitor Cell Deregulation Mediated by Serotonin.Frontiers in cell and developmental biology · 2021Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
Serotonin is a critical regulator of bone mass, fulfilling different functions depending on its site of synthesis. Brain-derived serotonin promotes osteoblast proliferation, whereas duodenal-derived serotonin suppresses it. To understand the molecular mechanisms of duodenal-derived serotonin action on osteoblasts, we explored its transcriptional mediation in mice. We found that the transcription factor FOXO1 is a crucial determinant of the effects of duodenum-derived serotonin on bone formation We identified two key FOXO1 complexes in osteoblasts, one with the transcription factor cAMP-responsive element-binding protein 1 (CREB) and another with activating transcription factor 4 (ATF4). Under normal levels of circulating serotonin, the proliferative activity of FOXO1 was promoted by a balance between its interaction with CREB and ATF4. However, high circulating serotonin levels prevented the association of FOXO1 with CREB, resulting in suppressed osteoblast proliferation. These observations identify FOXO1 as the molecular node of an intricate transcriptional machinery that confers the signal of duodenal-derived serotonin to inhibit bone formation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.