ArticleThe Journal of clinical investigation2017
Proprotein convertase furin regulates osteocalcin and bone endocrine function.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 75 citations in OpenAlex.
- Circulating FABP4, nesfatin-1, and osteocalcin concentrations in women with gestational diabetes mellitus: a meta-analysis.Lipids in health and disease · 2020Pooled it
- Osteocalcin Beyond Bone: Molecular Mechanisms, Endocrine Networks, and Translational Perspectives Across Metabolism, Neurobiology, and Chronic Disease.International journal of molecular sciences · 2026Review
- Specnuezhenide Alleviates Senile Osteoporosis by Activating TGR5/FXR Signaling in Bone Marrow Mesenchymal Stem Cells and RANKL-Induced Osteoclasts.Drug design, development and therapy · 2025Article
- Bidirectional crosstalk between the bone extracellular matrix and lysosomes in bone remodeling and osteoporosis.Frontiers in endocrinology · 2025Review
- Undercarboxylated OCN Inhibits Chondrocyte Hypertrophy and Osteoarthritis Development through GPRC6A/HIF-1α Cascade.International journal of biological sciences · 2025Article
- Host proteases: key regulators in viral infection and therapeutic targeting.Frontiers in immunology · 2025Review
- Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Dual-functional 3D-printed porous bioactive scaffold enhanced bone repair by promoting osteogenesis and angiogenesis.Materials today. Bio · 2024Article
- Pathological roles of bone marrow adipocyte-derived monocyte chemotactic protein-1 in type 2 diabetic mice.Cell death discovery · 2023Article
- Shikonin promotes rat periodontal bone defect repair and osteogenic differentiation of BMSCs by p38 MAPK pathway.Odontology · 2023Article
- Vitamin K-dependent carboxylation regulates CaCell reports · 2023Article
- Effect of oligonucleotide MT01 delivered by N-isopropylacrylamide modified polyethyleneimine for bone regeneration.Frontiers in bioengineering and biotechnology · 2023Article
- Mechanism and physical activities in bone-skeletal muscle crosstalk.Frontiers in endocrinology · 2023Review
- The proprotein convertase furin regulates the development of thymic epithelial cells to ensure central immune tolerance.iScience · 2022Article
- Osteocalcin and the physiology of danger.FEBS letters · 2022Review
- The Role of SIRT3 in the Osteoporosis.Frontiers in endocrinology · 2022Review
- Osteoinductivity and biomechanical assessment of a 3D printed demineralized bone matrix-ceramic composite in a rat spine fusion model.Acta biomaterialia · 2021Article
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Inhibition of furin by bone targeting superparamagnetic iron oxide nanoparticles alleviated breast cancer bone metastasis.Bioactive materials · 2021Article
- Pan-Cancer Analysis of FURIN as a Potential Prognostic and Immunological Biomarker.Frontiers in molecular biosciences · 2021Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteocalcin (OCN) is an osteoblast-derived hormone that increases energy expenditure, insulin sensitivity, insulin secretion, and glucose tolerance. The cDNA sequence of OCN predicts that, like many other peptide hormones, OCN is first synthesized as a prohormone (pro-OCN). The importance of pro-OCN maturation in regulating OCN and the identity of the endopeptidase responsible for pro-OCN cleavage in osteoblasts are still unknown. Here, we show that the proprotein convertase furin is responsible for pro-OCN maturation in vitro and in vivo. Using pharmacological and genetic experiments, we also determined that furin-mediated pro-OCN cleavage occurred independently of its γ-carboxylation, a posttranslational modification that is known to hamper OCN endocrine action. However, because pro-OCN is not efficiently decarboxylated and activated during bone resorption, inactivation of furin in osteoblasts in mice resulted in decreased circulating levels of undercarboxylated OCN, impaired glucose tolerance, and reduced energy expenditure. Furthermore, we show that Furin deletion in osteoblasts reduced appetite, a function not modulated by OCN, thus suggesting that osteoblasts may secrete additional hormones that regulate different aspects of energy metabolism. Accordingly, the metabolic defects of the mice lacking furin in osteoblasts became more apparent under pair-feeding conditions. These findings identify furin as an important regulator of bone endocrine function.
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