ArticleThe Journal of biological chemistry2011
The heparin-binding domain of IGFBP-2 has insulin-like growth factor binding-independent biologic activity in the growing skeleton.
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. An erratum has been issued. Cited by 37 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
37 citing papers in PubMed, 61 citations in OpenAlex.
- Insulin like growth factor - insulin like growth factor binding protein family in osteoporosis: mechanistic and clinical insights.Annals of medicine · 2026Review
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- Impaired neural circuitry of hippocampus in Pax2 nervous system-specific knockout mice leads to restricted repetitive behaviors.CNS neuroscience & therapeutics · 2024Article
- A Review on the Crosstalk between Insulin and Wnt/β-Catenin Signalling for Bone Health.International journal of molecular sciences · 2023Review
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- The Heartwarming Effect of Brown Adipose Tissue.Molecular pharmacology · 2022Review
- Insulin-like growth factors: Ligands, binding proteins, and receptors.Molecular metabolism · 2021Review
- Article
- AnStem cells international · 2021Review
- Osteosarcopenia in Reproductive-Aged Women with Polycystic Ovary Syndrome: A Multicenter Case-Control Study.The Journal of clinical endocrinology and metabolism · 2020Article
- Estrogen Stimulation of Pleiotrophin Enhances Osteoblast Differentiation and Maintains Bone Mass in IGFBP-2 Null Mice.Endocrinology · 2020Article
- Article
- IGFBP2 Plays an Essential Role in Cognitive Development during Early Life.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- A peptide containing the receptor binding site of insulin-like growth factor binding protein-2 enhances bone mass in ovariectomized rats.Bone research · 2018Article
- Insulin- like Growth Factor-Binding Protein Action in Bone Tissue: A Key Role for Pregnancy- Associated Plasma Protein-A.Frontiers in endocrinology · 2018Review
- Insulin growth factor binding protein 2 mediates the progression of lymphangioleiomyomatosis.Oncotarget · 2017Article
- The C-terminus of IGFBP-5 suppresses tumor growth by inhibiting angiogenesis.Scientific reports · 2016Article
- IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2016Article
- IGF-binding protein 2 is a candidate target of therapeutic potential in cancer.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2016Review
- Insulin/IGF signaling in Drosophila and other insects: factors that regulate production, release and post-release action of the insulin-like peptides.Cellular and molecular life sciences : CMLS · 2016Review
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
Insulin-like growth factor-binding protein 2 (IGFBP-2) is a member of a family of six highly conserved IGFBPs that are carriers for the insulin-like growth factors (IGFs). IGFBP-2 levels rise during rapid neonatal growth and at the time of peak bone acquisition. In contrast, Igfbp2(-/-) mice have low bone mass accompanied by reduced osteoblast numbers, low bone formation rates, and increased PTEN expression. In the current study, we postulated that IGFBP-2 increased bone mass partly through the activity of its heparin-binding domain (HBD). We synthesized a HBD peptide specific for IGFBP-2 and demonstrated in vitro that it rescued the mineralization phenotype of Igfbp2(-/-) bone marrow stromal cells and calvarial osteoblasts. Consistent with its cellular actions, the HBD peptide ex vivo stimulated metacarpal periosteal expansion. Furthermore, administration of HBD peptide to Igfbp2(-/-) mice increased osteoblast number, suppressed marrow adipogenesis, restored trabecular bone mass, and reduced bone resorption. Skeletal rescue in the Igfbp2(-/-) mice was characterized by reduced PTEN expression followed by enhanced Akt phosphorylation in response to IGF-I and increased β-catenin signaling through two mechanisms: 1) stimulation of its cytosolic accumulation and 2) increased phosphorylation of serine 552. We conclude that the HBD peptide of IGFBP-2 has anabolic activity by activating IGF-I/Akt and β-catenin signaling pathways. These data support a growing body of evidence that IGFBP-2 is not just a transport protein but rather that it functions coordinately with IGF-I to stimulate growth and skeletal acquisition.
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What OpenQuestion holds
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.