ArticleThe Journal of biological chemistry2011
Foxo1 mediates insulin-like growth factor 1 (IGF1)/insulin regulation of osteocalcin expression by antagonizing Runx2 in osteoblasts.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 80 citations in OpenAlex.
- Critical role of AKT protein in myeloma-induced osteoclast formation and osteolysis.The Journal of biological chemistry · 2013Trial
- Heterogeneous dental follicle cells and the regeneration of complex periodontal tissues.Tissue engineering. Part A · 2012Trial
- Homocysteine-induced bone formation dysfunction reversed by icariin via the AKT/FOXO1 signaling pathway.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Cellular signaling crosstalk between osteoporosis and diabetes: Common mechanisms and therapeutic targets (Review).Biomedical reports · 2026Review
- Mediating effect of osteocalcin underlying the link between insulin-like growth factor-I and gestational diabetes mellitus.BMC pregnancy and childbirth · 2025Article
- Osteocalcin in Infancy and Early Childhood and Its Correlation With Later Growth and Body Composition: A Longitudinal Birth Cohort Study.Clinical endocrinology · 2025Article
- Integrative genomic analysis and diagnostic modeling of osteoporosis: unraveling the interplay of autophagy, osteogenesis, adipogenesis, and immune infiltration.Frontiers in medicine · 2025Article
- Bone metabolism associated with annual antler regeneration: a deer insight into osteoporosis reversal.Biology direct · 2024Review
- Forkhead box O proteins: steering the course of stem cell fate.Cell regeneration (London, England) · 2024Review
- The FoxO1-ATGL axis alters milk lipolysis homeostasis through PI3K/AKT signaling pathway in dairy goat mammary epithelial cells.Journal of animal science · 2023Article
- Stimulation of the Runx2 P1 promoter by collagen-derived dipeptide prolyl-hydroxyproline bound to Foxg1 and Foxo1 in osteoblasts.Bioscience reports · 2021Article
- Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.Nature communications · 2021Article
- The Development of Molecular Biology of Osteoporosis.International journal of molecular sciences · 2021Review
- In vitro osteogenic induction of human adipose stem cells co-treated with betaine/osteogenesis differentiation medium.Molecular biology research communications · 2021Article
- Kindlin-2 modulates MafA and β-catenin expression to regulate β-cell function and mass in mice.Nature communications · 2020Article
- The Roles of FoxO Transcription Factors in Regulation of Bone Cells Function.International journal of molecular sciences · 2020Review
- Ginsenoside Rb1 prevents steroid‑induced avascular necrosis of the femoral head through the bone morphogenetic protein‑2 and vascular endothelial growth factor pathway.Molecular medicine reports · 2019Article
- Bidirectional regulation of osteogenic differentiation by the FOXO subfamily of Forkhead transcription factors in mammalian MSCs.Cell proliferation · 2019Review
- Expression of the ectodomain-releasing protease ADAM17 is directly regulated by the osteosarcoma and bone-related transcription factor RUNX2.Journal of cellular biochemistry · 2018Article
- PTEN Loss Promotes Intratumoral Androgen Synthesis and Tumor Microenvironment Remodeling via Aberrant Activation of RUNX2 in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In this study, we determined the molecular mechanisms whereby forkhead transcription factor Foxo1, a key downstream signaling molecule of insulin-like growth factor 1 (IGF1)/insulin actions, regulates Runx2 activity and expression of the mouse osteocalcin gene 2 (Bglap2) in osteoblasts in vitro. We showed that Foxo1 inhibited Runx2-dependent transcriptional activity and osteocalcin mRNA expression and Bglap2 promoter activity in MC-4 preosteoblasts. Co-immunoprecipitation assay showed that Foxo1 physically interacted with Runx2 via its C-terminal region in osteoblasts or when co-expressed in COS-7 cells. Electrophoretic mobility shift assay demonstrated that Foxo1 suppressed Runx2 binding to its cognate site within the Bglap2 promoter. IGF1 and insulin prevented Foxo1 from inhibiting Runx2 activity by promoting Foxo1 phosphorylation and nuclear exclusion. In contrast, a neutralizing anti-IGF1 antibody decreased Runx2 activity and osteocalcin expression in osteoblasts. Chromatin immunoprecipitation assay revealed that IGF1 increased Runx2 interaction with a chromatin fragment of the proximal Bglap2 promoter in a PI3K/AKT-dependent manner. Conversely, knockdown of Foxo1 increased Runx2 interaction with the promoter. This study establishes that Foxo1 is a novel negative regulator of osteoblast-specific transcription factor Runx2 and modulates IGF1/insulin-dependent regulation of osteocalcin expression in osteoblasts.
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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.