ReviewEndocrinology2021
Explaining Divergent Observations Regarding Osteocalcin/GPRC6A Endocrine Signaling.
Review in Endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 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
20 citing papers in PubMed, 28 citations in OpenAlex.
- Comparison of cheese with and withoutJournal of the International Society of Sports Nutrition · 2025Trial
- The relationship between circulating osteocalcin and muscle mass measurements in humans: A systematic review and meta-analysis.Sports medicine and health science · 2026Review
- Molecular mechanisms, therapeutic strategies, and inter-organ fibrosis crosstalk of Gla proteins in cardiovascular disease.Communications biology · 2026Review
- The bone-cerebrovascular axis: effects of bone aging on neurovascular dysfunction and neurodegeneration.The Journal of clinical investigation · 2026Review
- Testosterone and cancers: biological functions, molecular mechanisms and therapy.Molecular cancer · 2026Review
- Bone-derived factors mediate crosstalk between skeletal and extra-skeletal organs.Bone research · 2025Review
- A Study of the Effects of Oleuropein and Polydatin Association on Muscle and Bone Metabolism.Biomolecules · 2025Article
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- The Role of Bone-Derived Osteocalcin in Testicular Steroidogenesis: Contributing Factor to Male Fertility.Diseases (Basel, Switzerland) · 2024Review
- Emerging role of liver-bone axis in osteoporosis.Journal of orthopaedic translation · 2024Review
- Osteocalcin binds to a GPRC6A Venus fly trap allosteric site to positively modulate GPRC6A signaling.FASEB bioAdvances · 2024Article
- Bone-muscle crosstalk under physiological and pathological conditions.Cellular and molecular life sciences : CMLS · 2024Review
- Osteocalcin: Beyond Bones.Endocrinology and metabolism (Seoul, Korea) · 2024Review
- Osteocalcin of maternal and embryonic origins synergize to establish homeostasis in offspring.EMBO reports · 2024Article
- Osteocalcin and Its Potential Functions for Preventing Fatty Liver Hemorrhagic Syndrome in Poultry.Animals : an open access journal from MDPI · 2023Review
- Effect on bone anabolic markers of daily cheese intake with and without vitamin KBMJ nutrition, prevention & health · 2022Article
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- Embryonic osteocalcin signaling determines lifelong adrenal steroidogenesis and homeostasis in the mouse.The Journal of clinical investigation · 2022Article
- Association ofFrontiers in genetics · 2022Article
- Protein- and Calcium-Mediated GLP-1 Secretion: A Narrative Review.Advances in nutrition (Bethesda, Md.) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
A new schema proposes that the bone-derived osteocalcin (Ocn) peptide hormone activates the G-protein-coupled receptor GPRC6A to directly regulate glucose and fat metabolism in liver, muscle, and fat, and to stimulate the release of metabolism-regulating hormones, including insulin, fibroblast growth factor 21, glucagon-like peptide 1, testosterone, and interleukin 6. Ocn/GPRC6A activation has also been implicated in cancer progression. GPRC6A is activated by cations, amino acids, and testosterone. The multiligand specificity, the regulation of energy metabolism in diverse tissues, and the coordinated release of metabolically active hormones make the GPRC6A endocrine networks unique. Recently, the significance of Ocn/GPRCA has been questioned. There is a lack of metabolic abnormalities in newly created genetically engineered Ocn- and Gprc6a-deficient mouse models. There are also paradoxical observations that GPRC6A may function as a tumor suppressor. In addition, discordant published studies have cast doubt on the function of the most prevalent uniquely human GPRC6A-KGKY polymorphism. Explanations for these divergent findings are elusive. We provide evidence that the metabolic susceptibility of genetically engineered Ocn- and Gprc6a-deficient mice is influenced by environmental challenges and genetic differences in mouse strains. In addition, the GPRC6A-KGKY polymorphism appears to be a gain-of-function variant. Finally, alternatively spliced isoforms of GPRC6A may alter ligand specificity and signaling that modulate oncogenic effects. Thus, genetic, post-translational and environmental factors likely account for the variable results regarding the functions of GPRC6A in animal models. Pending additional information, GPRC6A should remain a potential therapeutic target for regulating energy and fat metabolism, hormone production, and cancer progression.
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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.