Affinage

BGLAP

Osteocalcin · UniProt P02818

Round 2 corrected
Length
100 aa
Mass
11.0 kDa
Annotated
2026-04-28
130 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BGLAP encodes osteocalcin, a 49-amino-acid vitamin K-dependent secreted protein containing two gamma-carboxyglutamic acid residues that is synthesized by osteoblasts as a propeptide processed through the ER/Golgi secretory pathway, where it regulates hydroxyapatite mineral maturation, osteogenic differentiation, and endochondral ossification via BMP/TGF-β signaling (PMID:6967872, PMID:28106724, PMID:39337434). Transcription of BGLAP is activated by BMP2 through a Runx2→ATF6 axis and by autocrine 1,25-(OH)₂D₃ signaling in osteoblasts, with mRNA stability further controlled by YBX1-mediated m5C modification (PMID:22102412, PMID:17023519, PMID:40118929). Beyond its skeletal functions, osteocalcin acts as a circulating endocrine hormone: it stimulates testosterone biosynthesis in Leydig cells via a GPCR/CREB-dependent mechanism, promotes insulin secretion through GPRC6A on pancreatic β-cells, and crosses the blood-brain barrier to bind hippocampal GPR158, activating IP3/BDNF signaling that enhances memory and reduces anxiety in a circuit modulated by RbAp48 (PMID:21333348, PMID:21425331, PMID:24074871, PMID:28851741, PMID:30355501).

Mechanistic history

Synthesis pass · year-by-year structured walk · 11 steps
  1. 1980 High

    Resolving the primary structure of human osteocalcin established that it is a 49-residue polypeptide with two gamma-carboxyglutamic acid residues (Gla-21, Gla-24) and partial undercarboxylation at position 17, providing the molecular framework for understanding its calcium/mineral-binding properties.

    Evidence Protein purification from demineralized human bone with automated Edman sequencing and peptide mapping

    PMID:6967872

    Open questions at the time
    • Three-dimensional structure not determined
    • Functional significance of partial carboxylation at position 17 not established
  2. 1986 High

    Cloning the BGLAP gene revealed a four-exon structure encoding a 49-residue leader peptide (signal + pro sequence) homologous to Factor IX's gamma-carboxylation recognition domain, establishing the evolutionary basis for its vitamin K-dependent post-translational modification.

    Evidence cDNA library cloning from osteosarcoma cells, DNA sequencing, Northern/Southern blot analysis

    PMID:3019668

    Open questions at the time
    • Promoter regulatory elements not yet characterized
    • Hormonal regulation of transcription not dissected
  3. 1994 Medium

    Demonstrating that the osteocalcin propeptide localizes to ER/Golgi in osteoblasts and that the mature protein concentrates at the mineralization front established the secretory pathway processing of osteocalcin and its spatial coupling to active mineralization.

    Evidence Anti-propeptide immunofluorescence with monensin disruption, immunohistochemistry of fetal bone sections

    PMID:8086856

    Open questions at the time
    • Precise proteolytic processing enzymes not identified
    • Quantitative secretion kinetics not measured
  4. 2002 High

    Identification of the BMP2→Runx2→ATF6→BGLAP promoter transcriptional cascade revealed how osteoblast differentiation signals converge on osteocalcin expression, with ATF6 directly binding a TGACGT motif in the BGLAP promoter.

    Evidence Promoter-reporter assays, EMSA/ChIP, dominant-negative ATF6, Runx2−/− primary osteoblasts

    PMID:22102412

    Open questions at the time
    • Whether ATF6 regulation is conserved in human osteoblasts in vivo not confirmed
    • Interaction with other BGLAP promoter-binding factors (e.g., vitamin D receptor) not integrated
  5. 2006 High

    Showing that osteoblasts express 1α-hydroxylase and produce 1,25-(OH)₂D₃ autocrinally to induce BGLAP transcription identified a local vitamin D signaling loop driving osteocalcin expression independent of renal regulation.

    Evidence 1α-hydroxylase detection (RT-PCR, immunostaining) in human osteoblasts, 25-(OH)D₃ substrate conversion, osteocalcin mRNA and ALP induction

    PMID:17023519

    Open questions at the time
    • Direct VDR binding to BGLAP promoter not mapped in this study
    • In vivo quantitative contribution of autocrine vs. systemic vitamin D not resolved
  6. 2011 High

    Two landmark studies established osteocalcin as a bone-derived endocrine hormone by demonstrating that it stimulates testosterone biosynthesis in Leydig cells via a GPCR/CREB mechanism and that GPRC6A mediates osteocalcin signaling in pancreatic β-cells to stimulate insulin secretion.

    Evidence Osteoblast–Leydig cell coculture with conditional KO/KI mouse models (testosterone/CREB); Gprc6a transfection in HEK-293 cells (ERK/PKD1 phosphorylation) and Gprc6a−/− mice (insulin response)

    PMID:21333348 PMID:21425331

    Open questions at the time
    • Whether GPRC6A also mediates the testicular response not tested
    • Undercarboxylated vs. carboxylated osteocalcin receptor selectivity not fully resolved
    • Human genetic evidence for endocrine functions lacking
  7. 2013 High

    Demonstrating that osteocalcin crosses the blood-brain barrier, modulates monoamine and GABA neurotransmitter synthesis, and is required for normal brain development (with maternal osteocalcin crossing the placenta) expanded osteocalcin's endocrine repertoire to include central nervous system regulation.

    Evidence Osteocalcin−/− mouse model with maternal/postnatal osteocalcin delivery, BBB crossing assay, neurotransmitter measurements, behavioral assays

    PMID:24074871

    Open questions at the time
    • Brain receptor not yet identified in this study
    • Human relevance of maternal–fetal osteocalcin transfer not established
  8. 2017 High

    Identification of GPR158 as the hippocampal receptor for osteocalcin, activating IP3 and BDNF signaling, and demonstration that osteocalcin knockdown impairs mineral maturation in human MSCs, deepened both the neural and skeletal mechanistic understanding of osteocalcin.

    Evidence Gpr158−/− mice with electrophysiology, IP3/BDNF measurement, behavioral rescue in aged mice; siRNA knockdown in human MSCs with Raman spectroscopy

    PMID:28106724 PMID:28851741

    Open questions at the time
    • GPR158 downstream signaling cascade beyond IP3/BDNF not fully mapped
    • Structural basis of osteocalcin–GPR158 interaction unknown
  9. 2018 Medium

    Discovery of a bidirectional feedback loop between RbAp48 and the osteocalcin/GPR158 pathway in the hippocampus provided a circuit-level mechanism for age-related memory decline and its rescue by osteocalcin.

    Evidence RbAp48 viral inhibition in hippocampus, OCN/GPR158 pathway manipulation, discrimination memory behavioral assays in aged mice

    PMID:30355501

    Open questions at the time
    • Molecular mechanism by which RbAp48 controls GPR158 expression not defined
    • Whether the feedback loop operates in humans not tested
  10. 2024 Medium

    A CRISPR/Cas9 Bglap/Bglap2 double-knockout mouse model revealed that osteocalcin regulates chondrocyte differentiation and endochondral ossification timing through BMP/TGF-β pathways, expanding its skeletal role beyond mineralization to cartilage-to-bone transition.

    Evidence Double KO mouse with microCT, histology, BMSC chondrogenic assays, transcriptional pathway analysis

    PMID:39337434

    Open questions at the time
    • Whether osteocalcin acts directly on chondrocytes or indirectly via paracrine signals not distinguished
    • Specific BMP/TGF-β pathway components mediating this effect not identified
  11. 2025 Medium

    Identification of YBX1-mediated m5C modification as a post-transcriptional stabilizer of BGLAP mRNA revealed a new layer of osteocalcin regulation linking epitranscriptomic control to osteogenic differentiation.

    Evidence YBX1 knockdown in MC3T3 cells, meRIP for m5C, RIP/luciferase for YBX1–BGLAP interaction, OVX mouse rescue

    PMID:40118929

    Open questions at the time
    • Specific m5C sites on BGLAP mRNA not mapped
    • Whether m5C modification affects translation efficiency in addition to stability not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of osteocalcin binding to its receptors (GPRC6A, GPR158), the relative endocrine contributions of undercarboxylated versus carboxylated forms, whether the endocrine functions observed in mice translate to humans, and how transcriptional and epitranscriptomic regulatory inputs are integrated in vivo.
  • No co-crystal or cryo-EM structure of osteocalcin–receptor complexes
  • Human genetic loss-of-function data for BGLAP endocrine phenotypes lacking
  • In vivo relative importance of carboxylation state for each receptor unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 4 GO:0060089 molecular transducer activity 3
Localization
GO:0005576 extracellular region 5 GO:0031012 extracellular matrix 3 GO:0005783 endoplasmic reticulum 1 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-112316 Neuronal System 3 R-HSA-1430728 Metabolism 2
Partners
ATF6GPR158GPRC6ARBBP4RUNX2SP7YBX1

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1980 Human bone Gla protein (osteocalcin/BGLAP) was isolated and sequenced as a 49-amino-acid single polypeptide chain containing 2 residues of gamma-carboxyglutamic acid (at positions 21 and 24, with position 17 only ~9% carboxylated) and a single disulfide bond, establishing partial undercarboxylation as a structural feature. Protein purification from demineralized bone, automated Edman sequence analysis, tryptic/S. aureus protease digestion peptide mapping The Journal of biological chemistry High 6967872
1986 The human BGLAP gene was isolated using rat/mouse osteosarcoma cDNA probes. Sequence analysis showed the cDNA encodes the mature protein plus a 49-amino-acid leader peptide containing a hydrophobic signal sequence and a pro sequence. The gene contains four exons; the exon encoding the putative gamma-carboxylation recognition site in the leader peptide shows homology with Factor IX, suggesting a common ancestral sequence. BGP mRNA levels in osteoblastic cells are modulated by hormones. cDNA library cloning from rat/mouse osteosarcoma cells, DNA sequencing, Southern blotting, Northern blotting, genomic library screening The EMBO journal High 3019668
1994 Pro-BGP (the propeptide-containing precursor of osteocalcin) was detected intracellularly in osteoblasts associated with the ER and Golgi secretory pathway; monensin disrupted the intracellular pattern, confirming transit through the secretory pathway. Antibodies to the propeptide strongly labeled newly embedded osteocytes in fetal bone tissue, while antibodies to the mature protein primarily stained the mineralization front, suggesting osteocalcin synthesis is a late event in osteoblastic development. Anti-propeptide antibody generation (ELISA characterization), immunoperoxidase staining, immunofluorescence with monensin treatment, immunohistochemistry of fetal bone sections Bone and mineral Medium 8086856
1999 The human osteocalcin gene (BGLAP) was refined to chromosomal region 1q25-1q31 by genetic and physical mapping. A new microsatellite marker D1S3737 tightly linked to BGLAP showed a significant association with bone mineral density status in postmenopausal women, suggesting genetic variation at the BGLAP locus influences BMD. Somatic cell hybridization refinement, microsatellite marker development, PCR-RFLP genotyping, logistic regression association analysis Genomics Low 10486212
2002 BMP2 induces osteoblast differentiation through a Runx2-dependent upregulation of ATF6 (a UPR bZIP transcription factor), which then directly binds a putative ATF6 motif (TGACGT, -1126 to -1121 bp) in the osteocalcin (BGLAP) promoter to activate its transcription. Runx2 directly binds the OSE2 motif of the Atf6 promoter; ATF6 activation was absent in Runx2-/- primary calvarial osteoblasts and restored by Runx2 overexpression. Dominant-negative ATF6 blocked BMP2- or Runx2-induced osteocalcin expression and matrix mineralization. Promoter-reporter luciferase assays, EMSA/ChIP for Runx2 binding to Atf6 promoter, dominant-negative ATF6 overexpression, Runx2-/- primary osteoblasts, RT-PCR, ALP and Alizarin red staining The Journal of biological chemistry High 22102412
2006 Human osteoblasts express 1alpha-hydroxylase and can convert 25-(OH)D3 to 1alpha,25-(OH)2D3 in an autocrine/paracrine manner, which is sufficient to induce osteocalcin (BGLAP) mRNA expression, ALP activity, and mineralization in osteoblasts. Classical renal regulators (PTH, calcium) do not regulate 1alpha-hydroxylase in osteoblasts, whereas IL-1β strongly induces it. 1alpha-hydroxylase expression (RT-PCR, immunostaining), incubation with 25-(OH)D3 substrate, measurement of osteocalcin mRNA and ALP activity, mineralization assay FASEB journal High 17023519
2007 BGLAP (osteocalcin) is expressed in pancreatic cancer cell lines and PDAC tissues, and its silencing via siRNA reduced both cell proliferation and invasion in pancreatic cancer cell lines, indicating a functional role in promoting cancer cell growth and invasion through autocrine/paracrine mechanisms. TNFα reduced BGLAP mRNA and protein levels in these cells. Quantitative RT-PCR, immunohistochemistry, immunocytochemistry, enzyme immunoassay (secreted protein), siRNA knockdown, cell proliferation and invasion assays Molecular cancer Medium 18163903
2011 Osteocalcin (encoded by BGLAP) acts as an osteoblast-derived hormone that regulates male fertility: osteoblasts induce testosterone production by Leydig cells in the testes through osteocalcin binding to a G protein-coupled receptor on Leydig cells, activating CREB-dependent expression of testosterone biosynthesis enzymes and promoting germ cell survival. Osteocalcin had no influence on estrogen production by ovaries in coculture. Osteoblast-Leydig cell coculture assays, cell-specific loss-of-function and gain-of-function mouse models (conditional knockouts/knockins), testosterone/enzyme expression readouts, CREB phosphorylation analysis Cell High 21333348
2011 GPRC6A mediates osteocalcin (BGLAP product) signaling in pancreatic β-cells: transfection of HEK-293 cells with Gprc6a conferred dose-dependent responses to osteocalcin as measured by PKD1 and ERK phosphorylation. Intraperitoneal osteocalcin stimulated ERK and raised serum insulin in wild-type but not Gprc6a-/- mice, identifying GPRC6A as a receptor for osteocalcin in the bone-pancreas endocrine loop. Gprc6a transfection in HEK-293 cells, ERK/PKD1 phosphorylation assays, Gprc6a-/- mouse IP osteocalcin injection, serum insulin measurement Journal of bone and mineral research High 21425331
2013 Osteocalcin (BGLAP) crosses the blood-brain barrier, binds to neurons in the brainstem, midbrain, and hippocampus, enhances synthesis of monoamine neurotransmitters, inhibits GABA synthesis, prevents anxiety/depression, and favors learning and memory. Maternal osteocalcin crosses the placenta and prevents neuronal apoptosis in embryos before they synthesize osteocalcin. The severity of neuroanatomical defects in Osteocalcin-/- offspring depends on maternal genotype; delivering osteocalcin to pregnant Osteocalcin-/- mothers rescues brain defects in offspring. Osteocalcin-/- mouse model, in vivo osteocalcin delivery experiments (maternal and postnatal), BBB crossing assay, neuronal binding studies, neurotransmitter synthesis measurements, behavioral assays (memory/anxiety), neuroanatomical analysis Cell High 24074871
2017 GPR158, an orphan G protein-coupled receptor expressed in CA3 neurons of the hippocampus, transduces osteocalcin's regulation of hippocampal-dependent memory. Osteocalcin binding to GPR158 activates inositol 1,4,5-trisphosphate signaling and upregulates BDNF. Genetic, electrophysiological, molecular, and behavioral assays confirmed that peripheral delivery of osteocalcin to aged mice improves memory and reduces anxiety in an OCN-sufficient manner dependent on GPR158. Genetic loss-of-function (Gpr158-/- mice), electrophysiological assays, molecular signaling (IP3/BDNF measurement), peripheral osteocalcin delivery in aged mice, behavioral assays (memory/anxiety) The Journal of experimental medicine High 28851741
2017 Osteocalcin knockdown in human mesenchymal stromal cells (MSCs) delayed mineral species maturation (assessed by Raman spectroscopy) and reduced total hydroxyapatite content. Osteocalcin KD also downregulated RUNX2, ALP, type I collagen, and osteonectin expression during osteogenic differentiation, while osterix was upregulated, establishing osteocalcin as a regulator of mineral maturation and osteogenic differentiation in MSCs. Osteocalcin siRNA knockdown in human MSCs, Raman spectroscopy for mineral species analysis, RT-PCR for osteogenic marker genes, osterix/RUNX2 protein expression International journal of molecular sciences Medium 28106724
2018 RbAp48 controls expression of BDNF and GPR158, both components of osteocalcin (OCN) signaling in the mouse hippocampus. Inhibition of RbAp48 in hippocampal formation blocked OCN's beneficial effects on cognition and caused discrimination memory deficits. Disruption of OCN/GPR158 signaling led to downregulation of RbAp48, and activation of the OCN/GPR158 pathway increased RbAp48 expression in the aged dentate gyrus and rescued age-related memory loss, defining a bidirectional feedback loop. RbAp48 inhibition in hippocampus (viral vector), OCN/GPR158 pathway manipulation, behavioral assays (discrimination memory), Western blot for protein expression, aged mouse models Cell reports Medium 30355501
2019 In zebrafish, sp7 (osterix) directly regulates bglap (osteocalcin) expression through Sp7-binding sites on the bglap promoter. CRISPR/Cas9 knockout of sp7 led to significantly reduced bglap expression and impaired bone mineralization and abnormal tooth development. Cell transfection experiments confirmed Sp7 directly activates bglap transcription via its promoter binding sites. CRISPR/Cas9 sp7 knockout in zebrafish, quantitative RT-PCR, cell transfection with promoter-reporter constructs, phenotypic analysis of bone mineralization and tooth development Journal of biosciences Medium 31894108
2024 Using a CRISPR/Cas9 bglap-bglap2 double knockout (OCNem) mouse model, osteocalcin (OCN) was shown to regulate chondrocyte differentiation and endochondral ossification. OCNem mice showed delayed primary and secondary ossification centers, increased cartilage length in growth plates and hypertrophic zones, and increased chondrogenic differentiation capacity of BMSCs. Mechanistically, BMP and TGF-β signaling pathways were highly affected in OCNem BMSCs; OCN deficiency increased chondrocyte differentiation and postponed vascularization. CRISPR/Cas9 double KO mouse model, microCT, histology, BMSC chondrogenic differentiation assays, transcriptional network analysis (BMP/TGF-β pathway gene expression) International journal of molecular sciences Medium 39337434
2025 YBX1 binds to BGLAP mRNA and promotes its m5C (5-methylcytosine) RNA modification, thereby stabilizing BGLAP mRNA. Isoimperatorin (ISO) promotes osteogenic differentiation by increasing YBX1 expression, which enhances BGLAP mRNA stability through m5C modification. YBX1 knockdown inhibited osteogenic differentiation, reduced BGLAP m5C levels, and restored osteoporosis in OVX mice treated with ISO, placing this pathway: ISO → YBX1 upregulation → BGLAP m5C modification → mRNA stability → osteogenesis. YBX1 knockdown in MC3T3 cells, methylated RNA immunoprecipitation (meRIP) for m5C, RIP and luciferase reporter assay for YBX1-BGLAP interaction, biolayer interferometry (ISO-YBX1 binding), OVX mouse model, microCT, ALP activity, Alizarin red staining Scientific reports Medium 40118929
2022 BMSC-derived exosomes inhibit vascular smooth muscle cell calcification by transferring miR-15a/15b/16, which target the 3'UTR of NFATc3 mRNA. Downregulation of NFATc3 inhibits osteocalcin (OCN/BGLAP) expression, thereby suppressing osteogenic transdifferentiation of VSMCs. Dual-luciferase reporter assays confirmed direct miR-15a/15b/16 targeting of NFATc3, and NFATc3 knockdown reduced OCN expression and calcification. BMSC exosome isolation, miRNA overexpression/inhibition, dual-luciferase reporter assays (miRNA-target 3'UTR), NFATc3 siRNA knockdown, Western blot, Alizarin red staining, AKP activity Biochemical and biophysical research communications Medium 36257194

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
2020 A reference map of the human binary protein interactome. Nature 849 32296183
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2011 Endocrine regulation of male fertility by the skeleton. Cell 472 21333348
2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature genetics 406 20139978
1986 Isolation of the human gene for bone gla protein utilizing mouse and rat cDNA clones. The EMBO journal 375 3019668
2013 Maternal and offspring pools of osteocalcin influence brain development and functions. Cell 337 24074871
2008 Association between serum osteocalcin and markers of metabolic phenotype. The Journal of clinical endocrinology and metabolism 302 19088165
2009 Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 287 19063687
2017 Gpr158 mediates osteocalcin's regulation of cognition. The Journal of experimental medicine 240 28851741
1980 Isolation and sequence of the vitamin K-dependent protein from human bone. Undercarboxylation of the first glutamic acid residue. The Journal of biological chemistry 239 6967872
2004 A conserved Mis12 centromere complex is linked to heterochromatic HP1 and outer kinetochore protein Zwint-1. Nature cell biology 222 15502821
2010 Human POGZ modulates dissociation of HP1alpha from mitotic chromosome arms through Aurora B activation. Nature cell biology 217 20562864
2017 Osteocalcin Mediates Biomineralization during Osteogenic Maturation in Human Mesenchymal Stromal Cells. International journal of molecular sciences 202 28106724
2005 Binding of pRB to the PHD protein RBP2 promotes cellular differentiation. Molecular cell 196 15949438
2011 GPRC6A mediates responses to osteocalcin in β-cells in vitro and pancreas in vivo. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 183 21425331
2009 The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes/metabolism research and reviews 176 19877133
1996 CD66a (BGP), an adhesion molecule of the carcinoembryonic antigen family, is expressed in epithelium, endothelium, and myeloid cells in a wide range of normal human tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 169 8543780
2011 BMP2 protein regulates osteocalcin expression via Runx2-mediated Atf6 gene transcription. The Journal of biological chemistry 164 22102412
2006 Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 162 17023519
2002 Investigation of osteocalcin, osteonectin, and dentin sialophosphoprotein in developing human teeth. Bone 156 11856645
1988 Plasma BGP: an indicator of spontaneous bone loss and of the effect of oestrogen treatment in postmenopausal women. European journal of clinical investigation 151 2968266
2010 Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arteriosclerosis, thrombosis, and vascular biology 150 20395593
2010 Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. European journal of endocrinology 139 20501596
2008 Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clinica chimica acta; international journal of clinical chemistry 138 18657532
2014 Regulation of energy metabolism by the skeleton: osteocalcin and beyond. Archives of biochemistry and biophysics 136 24893146
2002 Differential regulation of Cbfa1/Runx2 and osteocalcin gene expression by vitamin-D3, dexamethasone, and local growth factors in primary human osteoblasts. Journal of cellular biochemistry 135 12112004
2015 An overview of the metabolic functions of osteocalcin. Reviews in endocrine & metabolic disorders 121 25577163
2002 Tests of linkage and/or association of genes for vitamin D receptor, osteocalcin, and parathyroid hormone with bone mineral density. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 107 11918225
1990 Molecular structure, chromosome assignment, and promoter organization of the human matrix Gla protein gene. The Journal of biological chemistry 105 2394711
2003 Telomerase accelerates osteogenesis of bone marrow stromal stem cells by upregulation of CBFA1, osterix, and osteocalcin. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 103 12674332
2021 Mitochondria-targeted therapeutics, MitoQ and BGP-15, reverse aging-associated meiotic spindle defects in mouse and human oocytes. Human reproduction (Oxford, England) 100 33367783
2009 Improvement of insulin sensitivity by a novel drug, BGP-15, in insulin-resistant patients: a proof of concept randomized double-blind clinical trial. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 98 19214941
1997 Differential expression of CD66a (BGP), a cell adhesion molecule of the carcinoembryonic antigen family, in benign, premalignant, and malignant lesions of the human mammary gland. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 92 9212821
2014 The small-molecule BGP-15 protects against heart failure and atrial fibrillation in mice. Nature communications 91 25489988
1987 A radioimmunoassay for bone Gla protein (BGP) in human plasma. Acta endocrinologica 81 3494371
2000 BGP-15, a nicotinic amidoxime derivate protecting heart from ischemia reperfusion injury through modulation of poly(ADP-ribose) polymerase. Biochemical pharmacology 79 10692558
2002 BGP-15 - a novel poly(ADP-ribose) polymerase inhibitor - protects against nephrotoxicity of cisplatin without compromising its antitumor activity. Biochemical pharmacology 78 11931842
1998 Dysregulated expression of CD66a (BGP, C-CAM), an adhesion molecule of the CEA family, in endometrial cancer. The American journal of pathology 78 9626043
1996 Biliary glycoprotein (BGP) expression on T cells and on a natural-killer-cell sub-population. International journal of cancer 70 8631584
2018 RbAp48 Protein Is a Critical Component of GPR158/OCN Signaling and Ameliorates Age-Related Memory Loss. Cell reports 65 30355501
2011 Membrane-lipid therapy in operation: the HSP co-inducer BGP-15 activates stress signal transduction pathways by remodeling plasma membrane rafts. PloS one 65 22174906
1993 Expression of the Bgp gene and characterization of mouse colon biliary glycoprotein isoforms. Gene 64 8500759
2009 BGP-15 inhibits caspase-independent programmed cell death in acetaminophen-induced liver injury. Toxicology and applied pharmacology 55 19931551
2006 Bgp, a secreted glycosaminoglycan-binding protein of Borrelia burgdorferi strain N40, displays nucleosidase activity and is not essential for infection of immunodeficient mice. Infection and immunity 54 16622242
2017 BGP-15 Protects against Oxidative Stress- or Lipopolysaccharide-Induced Mitochondrial Destabilization and Reduces Mitochondrial Production of Reactive Oxygen Species. PloS one 51 28046125
2012 BGP-15, a PARP-inhibitor, prevents imatinib-induced cardiotoxicity by activating Akt and suppressing JNK and p38 MAP kinases. Molecular and cellular biochemistry 49 22350755
2000 The adhesion molecule CEACAM1 (CD66a, C-CAM, BGP) is specifically expressed by the extravillous intermediate trophoblast. The American journal of pathology 46 10751340
2004 Bilateral generalized polymicrogyria (BGP): a distinct syndrome of cortical malformation. Neurology 45 15159468
1994 CD66 identifies the biliary glycoprotein (BGP) adhesion molecule: cloning, expression, and adhesion functions of the BGPc splice variant. Blood 44 8018919
1986 Serum bone gla protein (BGP) and other markers of bone mineral metabolism in postmenopausal osteoporosis. Calcified tissue international 42 3098385
1999 Osteocalcin: genetic and physical mapping of the human gene BGLAP and its potential role in postmenopausal osteoporosis. Genomics 41 10486212
1998 Expression of four CEA family antigens (CEA, NCA, BGP and CGM2) in normal and cancerous gastric epithelial cells: up-regulation of BGP and CGM2 in carcinomas. International journal of cancer 38 9533775
1999 Four carcinoembryonic antigen subfamily members, CEA, NCA, BGP and CGM2, selectively expressed in the normal human colonic epithelium, are integral components of the fuzzy coat. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 37 10436421
2024 BGP-15 alleviates LPS-induced depression-like behavior by promoting mitophagy. Brain, behavior, and immunity 36 38677623
2017 BGP-15 prevents the death of neurons in a mouse model of familial dysautonomia. Proceedings of the National Academy of Sciences of the United States of America 36 28439028
2017 BGP-15 Protects against Oxaliplatin-Induced Skeletal Myopathy and Mitochondrial Reactive Oxygen Species Production in Mice. Frontiers in pharmacology 34 28443020
2016 BGP-15 Improves Aspects of the Dystrophic Pathology in mdx and dko Mice with Differing Efficacies in Heart and Skeletal Muscle. The American journal of pathology 31 27750047
2015 Effect of Zinc Supplementation on GH, IGF1, IGFBP3, OCN, and ALP in Non-Zinc-Deficient Children. Journal of the American College of Nutrition 30 25759961
2014 Improvement of insulin sensitivity by a novel drug candidate, BGP-15, in different animal studies. Metabolic syndrome and related disorders 30 24386957
1993 Serum levels of bone Gla protein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegaly: effects of long-term octreotide treatment. Calcified tissue international 30 8481830
2012 The HSP co-inducer BGP-15 can prevent the metabolic side effects of the atypical antipsychotics. Cell stress & chaperones 29 22322357
1989 Bone GLA protein (BGP) levels and bone turnover in rheumatoid arthritis. British journal of rheumatology 29 2786438
1989 Immunocytochemical localization of BGP in human bones in various developmental stages and pathological conditions. Virchows Archiv. A, Pathological anatomy and histopathology 27 2508305
2004 Extracellular secretion of the Borrelia burgdorferi Oms28 porin and Bgp, a glycosaminoglycan binding protein. Infection and immunity 26 15501754
2019 Sp7/osterix positively regulates dlx2b and bglap to affect tooth development and bone mineralization in zebrafish larvae. Journal of biosciences 25 31894108
1990 Serum osteocalcin (BGP) levels in normal men: a longitudinal evaluation reveals an age-associated increase. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 25 2333785
1990 Influence of sex, age, and menopause in serum osteocalcin (BGP) levels. Klinische Wochenschrift 24 2135297
2019 Chaperone co-inducer BGP-15 mitigates early contractile dysfunction of the soleus muscle in a rat ICU model. Acta physiologica (Oxford, England) 23 31799784
2008 Excision of CN(-) and OCN(-) from acetamide and some amide derivatives triggered by low energy electrons. Physical chemistry chemical physics : PCCP 23 19030590
2012 Inhibition of cancer growth and induction of apoptosis by BGP-13 and BGP-15, new calcipotriene-derived vitamin D3 analogs, in-vitro and in-vivo studies. Investigational new drugs 22 22661288
2021 BGP-15 Protects against Heart Failure by Enhanced Mitochondrial Biogenesis and Decreased Fibrotic Remodelling in Spontaneously Hypertensive Rats. Oxidative medicine and cellular longevity 21 33564362
2007 BGLAP is expressed in pancreatic cancer cells and increases their growth and invasion. Molecular cancer 21 18163903
1995 CD49f (alpha 6 integrin) and CD66a (BGP) are specifically induced by retinoids during human monocytic differentiation. Leukemia 21 8609714
1991 The mouse biliary glycoprotein gene (Bgp): partial nucleotide sequence, expression, and chromosomal assignment. Genomics 21 1653760
1991 The putative role of members of the CEA-gene family (CEA, NCA an BGP) as ligands for the bacterial colonization of different human epithelial tissues. Zentralblatt fur Bakteriologie : international journal of medical microbiology 21 1718301
2022 Exosomes derived from bone marrow mesenchymal stem cells inhibit human aortic vascular smooth muscle cells calcification via the miR-15a/15b/16/NFATc3/OCN axis. Biochemical and biophysical research communications 19 36257194
2020 Fibroblast growth factor-4 maintains cellular viability while enhancing osteogenic differentiation of stem cell spheroids in part by regulating RUNX2 and BGLAP expression. Experimental and therapeutic medicine 19 32782511
1991 Serum bone Gla protein (BGP) during treatment of hyperthyroidism and hypothyroidism. A longitudinal study. Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme 18 1864560
1990 Measurement of serum bone gla-protein (BGP) in humans with an ovine BGP-based radioimmunoassay. Clinical chemistry 18 2208702
2018 BGP: identifying gene-specific branching dynamics from single-cell data with a branching Gaussian process. Genome biology 16 29843817
2017 RUNX-2, OPN and OCN expression induced by grey and white mineral trioxide aggregate in normal and hypertensive rats. International endodontic journal 16 29143348
2022 Identification of BgP, a Cutinase-Like Polyesterase From a Deep-Sea Sponge-Derived Actinobacterium. Frontiers in microbiology 15 35495686
2019 The Drug Candidate BGP-15 Delays the Onset of Diastolic Dysfunction in the Goto-Kakizaki Rat Model of Diabetic Cardiomyopathy. Molecules (Basel, Switzerland) 15 30736394
2018 The Borrelia burgdorferi Glycosaminoglycan Binding Protein Bgp in the B31 Strain Is Not Essential for Infectivity despite Facilitating Adherence and Tissue Colonization. Infection and immunity 15 29158428
1994 Production and characterization of an antibody against the human bone GLA protein (BGP/osteocalcin) propeptide and its use in immunocytochemistry of bone cells. Bone and mineral 15 8086856
2017 Chaperone co-inducer BGP-15 inhibits histone deacetylases and enhances the heat shock response through increased chromatin accessibility. Cell stress & chaperones 14 28474205
2006 Clinicopathological significance of BGP expression in non-small-cell lung carcinoma: relationship with histological type, microvessel density and patients' survival. Pathology 14 17393985
2004 Lack of association between the HindIII RFLP of the osteocalcin (BGP) gene and bone mineral density (BMD) in healthy pre- and postmenopausal Chinese women. Journal of bone and mineral metabolism 13 15108070
2003 Characterization of osteocalcin (BGP) and matrix Gla protein (MGP) fish specific antibodies: validation for immunodetection studies in lower vertebrates. Calcified tissue international 13 14668966
2001 Expression pattern of the adhesion molecule CEACAM1 (C-CAM, CD66a, BGP) in gestational trophoblastic lesions. International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists 13 11293162
1999 Difference in Bgp-independent fusion activity among mouse hepatitis viruses. Archives of virology 13 10550676
2020 The Paradoxical Effect of PARP Inhibitor BGP-15 on Irinotecan-Induced Cachexia and Skeletal Muscle Dysfunction. Cancers 12 33348673
2013 The Effects of Exenatide Microsphere on Serum BGP and ALP Levels in ZDF Rats after Implantation. Clinical implant dentistry and related research 12 24299614
2022 Cardioprotective Role of BGP-15 in Ageing Zucker Diabetic Fatty Rat (ZDF) Model: Extended Mitochondrial Longevity. Pharmaceutics 11 35213959
2020 Retinoprotection by BGP-15, a Hydroximic Acid Derivative, in a Type II Diabetic Rat Model Compared to Glibenclamide, Metformin, and Pioglitazone. International journal of molecular sciences 11 32204537
2002 Expression of the adhesion molecule CEACAM1 (CD66a, BGP, C-CAM) in breast cancer is associated with the expression of the tumor-suppressor genes Rb, Rb2, and p27. Virchows Archiv : an international journal of pathology 11 11964043
2018 BGP-15 improves contractile function of regenerating soleus muscle. Journal of muscle research and cell motility 10 29948663
2022 Possible Association Between Polymorphisms in ESR1, COL1A2, BGLAP, SPARC, VDR, and MMP2 Genes and Dental Fluorosis in a Population from an Endemic Region of West Bengal. Biological trace element research 9 35066749
2021 BGP-15 Inhibits Hyperglycemia-Aggravated VSMC Calcification Induced by High Phosphate. International journal of molecular sciences 9 34502172
2018 Identification of circulating murine CD34+OCN+ cells. Cytotherapy 9 30340982
2012 Expression patterns of runx2, sparc, and bgp during scale regeneration in the goldfish Carassius auratus. Journal of experimental zoology. Part B, Molecular and developmental evolution 9 22544716
2009 Mapping of IgE-binding regions on recombinant Cyn d 1, a major allergen from Bermuda Grass Pollen (BGP). Clinical and molecular allergy : CMA 9 19187539
2007 Contribution of the putative genetic factors and ANKH gene polymorphisms to variation of circulating calciotropic molecules, PTH and BGP. Human molecular genetics 9 17403715
2023 Benzo(ghi)perylene (BgP) a black tattoo ingredient induced skin toxicity via direct and indirect mode of DNA damage under UVA irradiation. Chemico-biological interactions 8 37150498
2023 PLGA/BGP/Nef porous composite restrains osteoclasts by inhibiting the NF-κB pathway, enhances IGF-1-mediated osteogenic differentiation and promotes bone regeneration. Journal of biological engineering 8 37461106
2023 Garlic extract enhances bioceramic bone scaffolds through upregulating ALP & BGLAP expression in hMSC-monocyte co-culture. Biomaterials advances 8 37742556
2021 Improved Survival and Retinal Function of Aging ZDF Rats in Long-Term, Uncontrolled Diabetes by BGP-15 Treatment. Frontiers in pharmacology 8 33935754
2013 Synergic insulin sensitizing effect of rimonabant and BGP-15 in Zucker-obese rats. Pathology oncology research : POR 8 23640247
2010 Association analysis of genetic polymorphisms and potential interaction of the osteocalcin (BGP) and ER-alpha genes with body mass index (BMI) in premenopausal Chinese women. Acta pharmacologica Sinica 8 20305683
2020 p38γ Activation and BGP (Biliary Glycoprotein) Induction in Primates at Risk for Inflammatory Bowel Disease and Colorectal Cancer-A Comparative Study with Humans. Vaccines 7 33276422
2024 REPRODUCTIVE AGEING: BGP-15 mitigates adverse impacts of aging on sperm quality, fertility, and offspring health in male mice. Reproduction (Cambridge, England) 6 39096934
2023 BGP-15 Protects against Doxorubicin-Induced Cell Toxicity via Enhanced Mitochondrial Function. International journal of molecular sciences 6 36982341
2022 Nicotinic-acid derivative BGP-15 improves diastolic function in a rabbit model of atherosclerotic cardiomyopathy. British journal of pharmacology 6 34811751
2022 Observation of the Curative Effect of Acupuncture for Tonifying Kidney and Removing Blood Stasis Combined with Radiofrequency Surgery in Patients with NSCLC and the Diagnostic Efficacy of Combined Detection of NTx, BGP, and CYFRA21-1 in the Occurrence of Bone Metastases. Contrast media & molecular imaging 6 36247849
2021 Modulation of Mitochondrial Quality Control Processes by BGP-15 in Oxidative Stress Scenarios: From Cell Culture to Heart Failure. Oxidative medicine and cellular longevity 6 33728024
2019 BGP-15 Protects Mitochondria in Acute, Acetaminophen Overdose Induced Liver Injury. Pathology oncology research : POR 6 31705481
2006 Influence of BGP-15, a nicotinic amidoxime derivative, on the vascularization and growth of murine hepatoma xenografts. Anticancer research 6 16619502
1989 BGP (osteocalcin, bone-Gla-protein) in involutional osteoporosis. Clinical rheumatology 6 2788062
2024 Novel Function of Osteocalcin in Chondrocyte Differentiation and Endochondral Ossification Revealed on a CRISPR/Cas9 bglap-bglap2 Deficiency Mouse Model. International journal of molecular sciences 5 39337434
2018 Cigarette Smoking is Associated with Decreased Bone Gla-protein (BGP) Levels in Hemodialysis Patients. Current vascular pharmacology 5 28933309
2014 Development of microfluidic-based assays to estimate the binding between osteocalcin (BGLAP) and fluorescent antibodies. Talanta 5 25476363
2010 Induction of apoptosis and inhibition of prostate and breast cancer growth by BGP-15, a new calcipotriene-derived vitamin D3 analog. Anti-cancer drugs 5 20335794
2002 BGP expression in gastric biopsies may predict the development of new lesions after local treatment for early gastric cancer. Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association 5 12378338
1986 Relationship between bone GLA-protein (BGP) and calcidiol (25-hydroxycalciferol) in serum of breast-fed infants. Endocrinologia experimentalis 5 3489605
2025 Isoimperatorin improves osteoporosis by increasing YBX1 expression to promote BGLAP m5C modification. Scientific reports 4 40118929
2023 Solution Studies of a Water-Stable, Trivalent Antimony Pnictogen Bonding Anion Receptor with High Binding Affinities for CN-, OCN-, and OAc. Inorganic chemistry 4 37499143
2011 The dynamic changes of circulating OCN+ cells versus insulinlike growth factor-I during primary healing of orthognathic surgeries. Oral surgery, oral medicine, oral pathology and oral radiology 4 22677019
2010 The effect of uremic toxin cyanate (OCN–) on anaerobic sulfur metabolism and prooxidative processes in the rat kidney: a protective role of lipoate. Human & experimental toxicology 4 21177730