ArticleNature communications2021
Endothelium-specific depletion of LRP1 improves glucose homeostasis through inducing osteocalcin.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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.
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Who cites it
18 citing papers in PubMed, 30 citations in OpenAlex.
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Interorgan Communications in Skeletal Pathophysiology: From Molecular Pathways to Multidisciplinary Therapies.Research (Washington, D.C.) · 2026Review
- Single-cell stemness analysis highlights Midkine-LRP1 pathway and identifies new bladder cancer subtypes.Cancer cell international · 2025Article
- Osteocalcin deficiency attenuates neointima formation after vascular injury in rat.BMC cardiovascular disorders · 2025Article
- Molecular Characterization and Expression of Lactoferrin Receptor (LfR) in Different Regions of the Brain Responding to Lactoferrin Intervention.Molecular neurobiology · 2025Article
- Emerging role of liver-bone axis in osteoporosis.Journal of orthopaedic translation · 2024Review
- Causal effect of blood osteocalcin on the risk of Alzheimer's disease and the mediating role of energy metabolism.Translational psychiatry · 2024Article
- CRAT links cholesterol metabolism to innate immune responses in the heart.Nature metabolism · 2023Article
- Review
- Article
- LDL receptor related protein 1 is an adverse prognostic biomarker that correlates with stromal remodeling and macrophages infiltration in bladder cancer.Frontiers in immunology · 2023Article
- The roles of hepatokine and osteokine in liver-bone crosstalk: Advance in basic and clinical aspects.Frontiers in endocrinology · 2023Review
- The Effects of Acute High-Intensity Interval Exercise and Hyperinsulinemic-Euglycemic Clamp on Osteoglycin Levels in Young and Middle-Aged Men.JBMR plus · 2022Article
- Neuroprotective Role of Lactoferrin during Early Brain Development and Injury through Lifespan.Nutrients · 2022Review
- Low total osteocalcin levels are associated with all-cause and cardiovascular mortality among patients with type 2 diabetes: a real-world study.Cardiovascular diabetology · 2022Article
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes.Diabetes, metabolic syndrome and obesity : targets and therapy · 2022Article
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
The vascular endothelium is present within metabolic organs and actively regulates energy metabolism. Here we show osteocalcin, recognized as a bone-secreted metabolic hormone, is expressed in mouse primary endothelial cells isolated from heart, lung and liver. In human osteocalcin promoter-driven green fluorescent protein transgenic mice, green fluorescent protein signals are enriched in endothelial cells lining aorta, small vessels and capillaries and abundant in aorta, skeletal muscle and eye of adult mice. The depletion of lipoprotein receptor-related protein 1 induces osteocalcin through a Forkhead box O -dependent pathway in endothelial cells. Whereas depletion of osteocalcin abolishes the glucose-lowering effect of low-density lipoprotein receptor-related protein 1 depletion, osteocalcin treatment normalizes hyperglycemia in multiple mouse models. Mechanistically, osteocalcin receptor-G protein-coupled receptor family C group 6 member A and insulin-like-growth-factor-1 receptor are in the same complex with osteocalcin and required for osteocalcin-promoted insulin signaling pathway. Therefore, our results reveal an endocrine/paracrine role of endothelial cells in regulating insulin sensitivity, which may have therapeutic implications in treating diabetes and insulin resistance through manipulating vascular endothelium.
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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.