ArticleThe Journal of cell biology2015
GGCX and VKORC1 inhibit osteocalcin endocrine functions.
Article in The Journal of cell biology, 2015. 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 35 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.
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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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- GGCX-Associated Phenotypes: An Overview in Search of Genotype-Phenotype Correlations.International journal of molecular sciences · 2017Pooled it
- Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study.European journal of clinical nutrition · 2018Trial
- Vitamin K-dependent carboxylation in osteoblasts regulates bone resorption through GAS6 in male mice.Bone research · 2026Article
- Vitamin K as an Endocrine Modulator: Mechanistic Links to Glucose Metabolism and Beyond.Nutrients · 2026Review
- LP533401 treatment alters vitamin K metabolism, bone Gla-OC/Glu-OC ratios, and improves mineral status of the skeleton in rats with chronic kidney disease.Frontiers in pharmacology · 2026Article
- Genome-wide association study of blood vitamin D metabolites and bone remodelling markers in pigs.BMC genomics · 2025Article
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- Association between surrogate marker of insulin resistance and bone mineral density in US adults without diabetes.Archives of osteoporosis · 2024Article
- Vitamin K-dependent carboxylation regulates CaCell reports · 2023Article
- Osteocalcin modulates parathyroid cell function in human parathyroid tumors.Frontiers in endocrinology · 2023Article
- New insights into vitamin K biology with relevance to cancer.Trends in molecular medicine · 2022Review
- The Role of GRP and MGP in the Development of Non-Hemorrhagic VKCFD1 Phenotypes.International journal of molecular sciences · 2022Review
- Skeletal endocrinology: where evolutionary advantage meets disease.Bone research · 2021Review
- Undercarboxylated osteocalcin inhibits the early differentiation of osteoclast mediated by Gprc6a.PeerJ · 2021Article
- Article
- Measurement of bioactive osteocalcin in humans using a novel immunoassay reveals association with glucose metabolism and β-cell function.American journal of physiology. Endocrinology and metabolism · 2020Article
- Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease.International journal of molecular sciences · 2019Review
- mTOR and ERK regulate VKORC1 expression in both hepatoma cells and hepatocytes which influence blood coagulation.Clinical and experimental medicine · 2019Article
- VKORC1L1, An Enzyme Mediating the Effect of Vitamin K in Liver and Extrahepatic Tissues.Nutrients · 2018Review
- Patterns of differential gene expression in a cellular model of human islet development, and relationship to type 2 diabetes predisposition.Diabetologia · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 4 institutions in 3 countries.
Funding
Abstract
Osteocalcin (OCN) is an osteoblast-derived hormone favoring glucose homeostasis, energy expenditure, male fertility, brain development, and cognition. Before being secreted by osteoblasts in the bone extracellular matrix, OCN is γ-carboxylated by the γ-carboxylase (GGCX) on three glutamic acid residues, a cellular process requiring reduction of vitamin K (VK) by a second enzyme, a reductase called VKORC1. Although circumstantial evidence suggests that γ-carboxylation may inhibit OCN endocrine functions, genetic evidence that it is the case is still lacking. Here we show using cell-specific gene inactivation models that γ-carboxylation of OCN by GGCX inhibits its endocrine function. We further show that VKORC1 is required for OCN γ-carboxylation in osteoblasts, whereas its paralogue, VKORC1L1, is dispensable for this function and cannot compensate for the absence of VKORC1 in osteoblasts. This study genetically and biochemically delineates the functions of the enzymes required for OCN modification and demonstrates that it is the uncarboxylated form of OCN that acts as a hormone.
Indexed as
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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.