ArticleGenes & development2010
CREB mediates brain serotonin regulation of bone mass through its expression in ventromedial hypothalamic neurons.
Article in Genes & development, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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Who cites it
66 citing papers in PubMed, 121 citations in OpenAlex.
- Neural regulation of bone: from central neural circuits to peripheral innervation of the skeletal stem cell niche.Bone research · 2026Review
- Advances in the regulation of bone metabolism by central nuclei: a new perspective on the brain-bone axis.Frontiers in neuroscience · 2026Review
- The therapeutic potential of descending regulatory pathways from brain to bone in osteoporosis: focusing on the brain-bone axis.Frontiers in endocrinology · 2026Review
- Targeting the central and peripheral nervous system to regulate bone homeostasis: mechanisms and potential therapies.Military Medical Research · 2025Review
- Strategies for promoting neurovascularization in bone regeneration.Military Medical Research · 2025Review
- Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression.Science advances · 2024Article
- Protective Effects of β-Blockers on Bone in Older Adults with Dementia.Calcified tissue international · 2024Article
- Experience-dependent, sexually dimorphic synaptic connectivity defined by sex-specific cadherin expression.bioRxiv : the preprint server for biology · 2024Article
- Skeletal interoception in osteoarthritis.Bone research · 2024Review
- Characteristics of bone metabolism in the male patients with diabetic neuropathy.Journal of the Chinese Medical Association : JCMA · 2024Article
- Secretin-dependent signals in the ventromedial hypothalamus regulate energy metabolism and bone homeostasis in mice.Nature communications · 2024Article
- Catgut embedding in acupoints combined with repetitive transcranial magnetic stimulation for the treatment of postmenopausal osteoporosis: study protocol for a randomized clinical trial.Frontiers in neurology · 2024Article
- Interoceptive regulation of skeletal tissue homeostasis and repair.Bone research · 2023Review
- Targeting CaMKK2 Inhibits Actin Cytoskeletal Assembly to Suppress Cancer Metastasis.Cancer research · 2023Article
- l-Type amino acid transporter 1 in hypothalamic neurons in mice maintains energy and bone homeostasis.JCI insight · 2023Article
- Skeletal interoception in bone homeostasis and pain.Cell metabolism · 2022Review
- A neuronal action of sirtuin 1 suppresses bone mass in young and aging mice.The Journal of clinical investigation · 2022Article
- Interactions between central nervous system and peripheral metabolic organs.Science China. Life sciences · 2022Review
- Peripheral nerves in the tibial subchondral bone : the role of pain and homeostasis in osteoarthritis.Bone & joint research · 2022Article
- Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.Nature communications · 2022Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Serotonin is a bioamine regulating bone mass accrual differently depending on its site of synthesis. It decreases accrual when synthesized in the gut, and increases it when synthesized in the brain. The signal transduction events elicited by gut-derived serotonin once it binds to the Htr1b receptor present on osteoblasts have been identified and culminate in cAMP response element-binding protein (CREB) regulation of osteoblast proliferation. In contrast, we do not know how brain-derived serotonin favors bone mass accrual following its binding to the Htr2c receptor on neurons of the hypothalamic ventromedial nucleus (VMH). We show here--through gene expression analysis, serotonin treatment of wild-type and Htr2c(-/-) hypothalamic explants, and cell-specific gene deletion in the mouse--that, following its binding to the Htr2c receptor on VMH neurons, serotonin uses a calmodulin kinase (CaMK)-dependent signaling cascade involving CaMKKβ and CaMKIV to decrease the sympathetic tone and increase bone mass accrual. We further show that the transcriptional mediator of these events is CREB, whose phosphorylation on Ser 133 is increased by CaMKIV following serotonin treatment of hypothalamic explants. A microarray experiment identified two genes necessary for optimum sympathetic activity whose expression is regulated by CREB. These results provide a molecular understanding of how serotonin signals in hypothalamic neurons to regulate bone mass accrual and identify CREB as a critical determinant of this function, although through different mechanisms depending on the cell type, neuron, or osteoblast in which it is expressed.
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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.