Affinage

BMP10

Bone morphogenetic protein 10 · UniProt O95393

Length
424 aa
Mass
48.0 kDa
Annotated
2026-06-09
69 papers in source corpus 33 papers cited in narrative 33 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMP10 is a TGF-β superfamily ligand that couples cardiac development to vascular homeostasis by signaling through the endothelial type I receptor ALK1, with BMPRII and ActRIIA as type II receptors, to phosphorylate Smad1/5/8 and activate BMP-responsive transcription (PMID:17068149). In the developing heart, Bmp10 is expressed in trabeculated ventricular myocardium and is transcriptionally driven by an SRF–myocardin complex acting at a non-consensus CArG element in its promoter; loss of BMP10 (or of upstream myocardin) elevates p57(kip2), collapses cardiomyocyte proliferation, and disrupts the cardiogenic factors NKX2.5 and MEF2C, defects rescuable by BMP10-conditioned medium (PMID:15073151, PMID:22996691, PMID:10072785). This cardiac role is non-redundant and cannot be substituted by the closely related BMP9, whereas the two ligands are functionally equivalent in vascular development where their roles are dictated by expression timing (PMID:23812757). Circulating bioactivity is carried largely by a disulfide-bonded BMP9–BMP10 heterodimer, and plasma from either Bmp10-KO or Bmp9-KO mice loses the ability to activate ALK1 (PMID:29789425). Cardiac-derived BMP10 is distributed by blood flow to maintain ALK1-dependent endothelial quiescence, limiting arterial caliber and endothelial proliferation, and BMP10 specifically (not BMP9) is indispensable for preventing arteriovenous malformations across multiple vascular beds (PMID:23863480, PMID:36348215). Structurally, ALK1 specificity arises from a tripartite recognition interface, while BMPRII engages a dynamic knuckle epitope, and bioactivity requires proprotein-convertase processing that converts a latent conformation into a receptor- and fibrillin-1-binding complex (PMID:32238803, PMID:35504921, PMID:39921464). Beyond canonical Smad signaling, BMP10 activates non-canonical STAT3 and MEKK4/p38–GADD45β pathways that underlie cardioprotection and endothelial transcriptional control (PMID:31712309, PMID:38439036). BMP10 also acts on vascular smooth muscle to maintain contractility and blood pressure via ALK1/SMAD7 (PMID:33334130), and in the liver hepatic stellate cells secrete GDF2/BMP10 to maintain Kupffer-cell and endothelial identity and prevent fibrosis (PMID:39453386). Human BMP10 loss-of-function variants are linked through family studies and reporter assays to dilated cardiomyopathy and patent ductus arteriosus (PMID:36673052, PMID:38322548).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 Medium

    Establishing where BMP10 acts in the embryo was the first step, localizing it to the developing heart and implicating it in trabeculation.

    Evidence In situ hybridization across mouse embryonic stages

    PMID:10072785

    Open questions at the time
    • No functional consequence demonstrated
    • Receptor and signaling pathway unknown at this stage
  2. 2004 High

    Genetic loss-of-function defined BMP10's essential developmental function in driving cardiomyocyte proliferation and chamber maturation by restraining p57(kip2).

    Evidence Bmp10-null mouse with proliferation phenotype and ex vivo conditioned-medium rescue

    PMID:15073151

    Open questions at the time
    • Receptor mediating cardiac proliferative effect not identified
    • Direct vs indirect regulation of p57kip2 unresolved
  3. 2006 High

    Identifying ALK1 with BMPRII/ActRIIA as the receptor system and Smad1/5/8 as the effector placed BMP10 in a defined endothelial signaling pathway controlling vascular cell behavior.

    Evidence Receptor siRNA knockdown, ALK1 ECD blockade, BRE-luciferase reporter, and endothelial migration/proliferation assays

    PMID:17068149

    Open questions at the time
    • Endogenous physiological source of ligand not addressed
    • Relationship to BMP9 not resolved
  4. 2012 High

    Defining the upstream transcriptional control showed myocardin/SRF directly activates Bmp10, embedding it in a cardiac transcriptional circuit.

    Evidence Myocd knockout mice, SRF-myocardin promoter binding, and ex vivo BMP10 rescue

    PMID:22996691

    Open questions at the time
    • Whether other transcription factors co-regulate Bmp10 unknown
  5. 2013 High

    Epistasis and ligand-swap genetics resolved that cardiac-derived, flow-distributed BMP10 is the physiological ALK1 ligand for vascular patterning, yet BMP10 holds a non-redundant cardiac role distinct from BMP9.

    Evidence Zebrafish loss-of-function/restoration with flow deprivation and mouse Bmp10(9/9) knock-in plus neutralizing antibodies

    PMID:23812757 PMID:23863480

    Open questions at the time
    • Molecular basis of cardiac-specific function not defined
    • Relative contribution of homodimer vs heterodimer in vivo unresolved
  6. 2018 High

    Discovery of the BMP9-BMP10 heterodimer identified the predominant circulating bioactive species that activates endothelial ALK1.

    Evidence Co-IP, heterodimer-specific ELISA, and ALK1 reporter/pSmad assays on KO mouse plasma

    PMID:29789425

    Open questions at the time
    • Relative in vivo contribution of heterodimer vs homodimers in specific vascular beds not quantified
  7. 2020 High

    Structural determination of BMP10:ALK1 and BMP10:BMPRII complexes provided an atomic mechanism for receptor specificity and assembly.

    Evidence X-ray crystallography with structure-guided mutagenesis and C2C12 signaling assays

    PMID:32238803 PMID:35504921

    Open questions at the time
    • Structure of full signaling-competent ternary complex on membranes not resolved
    • Conformational dynamics during receptor activation incompletely defined
  8. 2020 Medium

    Expanding effector repertoire and cellular targets showed BMP10 controls VSMC contractility/blood pressure, endothelial CCL2 repression, monocyte recruitment, and endocardial specification.

    Evidence Cell-specific mouse models, receptor/Smad siRNA dissection, blood-pressure measurement, hPSC differentiation, and adhesion assays

    PMID:28646109 PMID:32576665 PMID:33142114 PMID:33334130

    Open questions at the time
    • Context dependence of ALK1 vs ALK2 receptor usage incompletely mapped
    • Some readouts from single labs
  9. 2022 High

    Inducible and double-knockout studies established BMP10 as uniquely indispensable, rather than BMP9, for preventing arteriovenous malformations.

    Evidence Inducible Bmp10-KO, Bmp9-KO, double KO, and recombinant protein rescue across multiple vascular beds

    PMID:31828546 PMID:36348215

    Open questions at the time
    • Molecular basis for BMP10's superiority over BMP9 in AVM prevention unresolved
  10. 2024 High

    Hepatic stellate cells were identified as a liver source where GDF2/BMP10 maintain Kupffer cell and endothelial identity and prevent fibrosis, extending BMP10 function beyond heart and vasculature.

    Evidence Cell-type-specific conditional Gdf2/Bmp10 deletion and ALK1 reporter mice

    PMID:39453386

    Open questions at the time
    • Whether liver- vs heart-derived ligand pools are functionally separable not addressed
  11. 2024 Medium

    Phosphoproteomics defined a non-canonical SMAD-dependent MEKK4/p38-GADD45β pathway and STAT3 axis underlying endothelial transcriptional control and cardioprotection.

    Evidence Large-scale phosphoproteomics with siRNA/western validation and prior in vivo cardiac injury models

    PMID:31712309 PMID:38439036

    Open questions at the time
    • Receptor-proximal events branching canonical from non-canonical signaling not defined
  12. 2025 High

    Biophysical work resolved how proprotein-convertase processing and interchain disulfide geometry govern BMP10 bioactivity, secretion, and fibrillin-1 / ECM targeting.

    Evidence Molecular dynamics, TEM, circular dichroism, crystallography, AUC, and receptor/fibrillin-1 binding assays

    PMID:39793884 PMID:39921464

    Open questions at the time
    • In vivo significance of monomer vs dimer pools not established
    • Role of fibrillin-1 sequestration in tissue signaling not tested genetically
  13. 2023 Low

    Human family studies linked BMP10 loss-of-function variants to dilated cardiomyopathy and patent ductus arteriosus via loss of NKX2.5/TBX20 transactivation.

    Evidence Whole-exome sequencing and dual-luciferase transactivation reporter assays

    PMID:36673052 PMID:38322548 PMID:42261662

    Open questions at the time
    • Functional evidence limited to reporter assays for several variants
    • Causality not confirmed by animal models of the specific variants

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BMP10's distinct ligand forms (homodimer, heterodimer, monomer, processed vs latent) are spatially deployed to produce its non-redundant, tissue-specific roles in heart, vasculature, and liver remains unresolved.
  • No genetic dissection of homodimer vs heterodimer requirement per tissue
  • Mechanism of cardiac-specific function distinct from BMP9 unknown
  • Switch between canonical and non-canonical signaling outputs uncharacterized

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 3 GO:0060089 molecular transducer activity 3 GO:0098772 molecular function regulator activity 3
Localization
GO:0005576 extracellular region 2 GO:0005829 cytosol 1 GO:0005886 plasma membrane 1 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1266738 Developmental Biology 3 R-HSA-162582 Signal Transduction 3 R-HSA-1500931 Cell-Cell communication 2
Partners
ACVR2A/ACTRIIAALK1/ACVRL1BMP9/GDF2BMPR2ENGFBN1STAT3TCAP
Complex memberships
BMP10:ALK1:BMPRII receptor complexBMP9-BMP10 heterodimer

Evidence

Reading pass · 33 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 BMP10 (along with BMP9) is a high-affinity functional ligand for ALK1 in endothelial cells, inducing phosphorylation of Smad1/5/8 and activating a BMP response element (BRE). Silencing ALK1 or adding ALK1 extracellular domain abolishes this response. BMPRII and ActRIIA are required as type II receptors. Endoglin overexpression increases the response. BMP10 potently inhibits endothelial cell migration and growth via ALK1 signaling. siRNA knockdown of ALK1, BMPRII, ActRIIA; ALK1 extracellular domain addition; BRE-luciferase reporter assay; Smad1/5/8 phosphorylation assay; endothelial migration and proliferation assays Blood High 17068149
2004 BMP10 is essential for cardiac growth and chamber maturation during mouse cardiogenesis. BMP10-null mice show ectopic and elevated p57(kip2) expression and dramatically reduced cardiomyocyte proliferation at E9.0–E9.5. BMP10 is required to maintain normal expression of cardiogenic transcription factors NKX2.5 and MEF2C. BMP10-conditioned medium rescues proliferation defects in BMP10-null hearts cultured ex vivo. BMP10 knockout mouse generation; immunostaining for p57(kip2) and proliferation markers; ex vivo heart culture rescue with BMP10-conditioned medium; cardiogenic transcription factor expression analysis Development (Cambridge, England) High 15073151
1999 BMP10 expression is restricted to the developing heart in mouse embryos beginning at E9.0, initially localizing to the trabeculated ventricular chamber and bulbus cordis, later extending to the atrial wall after E12.5, indicating a role in cardiac trabeculation. In situ hybridization on mouse embryos at multiple developmental stages Mechanisms of development Medium 10072785
2012 Myocardin transcriptionally activates the Bmp10 gene by binding a serum response factor (SRF)-myocardin complex to a non-consensus CArG element in the Bmp10 promoter. Myocardin-null embryos show loss of BMP10 signaling, leading to defective cardiomyocyte proliferation, increased apoptosis, and elevated p57kip2. BMP10-conditioned medium rescues proliferation and p57kip2 defects in Myocd-/- hearts ex vivo. Cardiomyocyte-restricted and global Myocd knockout mice; Bmp10 promoter binding confirmed by SRF-myocardin complex; ex vivo rescue with BMP10-conditioned medium; expression analysis of p57kip2, NKX2.5, MEF2c The Journal of clinical investigation High 22996691
2013 Circulating cardiac-derived Bmp10 is the crucial ligand for endothelial Alk1 in zebrafish embryonic vascular development. Bmp10 deficiency phenocopies alk1 loss, with increased arterial endothelial cell number. Endothelial alk1 restoration alone (without Bmp10) fails to rescue Alk1 activity, indicating blood flow distributes Bmp10 to activate Alk1 and limit arterial caliber. Zebrafish genetic loss-of-function; endothelial alk1 restoration experiments; arterial caliber and endothelial cell number quantification; flow deprivation experiments Development (Cambridge, England) High 23863480
2013 BMP9 and BMP10 are functionally equivalent physiological ligands for ALK1 in vascular development, with their in vivo roles dictated by timing of expression. However, BMP10 has an exclusive function in cardiac development that cannot be substituted by BMP9, established by generating Bmp10(9/9) knock-in mice where BMP9 coding sequence replaces BMP10. Conventional knockout and Bmp10(9/9) knock-in mouse; neutralizing antibodies against BMP9 or BMP10; vascular and cardiac phenotype analysis Proceedings of the National Academy of Sciences of the United States of America High 23812757
2018 BMP9 and BMP10 form a disulfide-bonded heterodimer in vitro and in vivo (detected in human and mouse plasma by specific ELISA). This BMP9-BMP10 heterodimer accounts for most of the circulating BMP biological activity that activates ALK1 on endothelial cells and phospho-Smad1-5. Plasma from either Bmp10-KO or Bmp9-KO mice completely lacks the ability to activate ALK1. Hepatic stellate cells in the liver are identified as a potential source of the heterodimer. Co-transfection and co-immunoprecipitation; heterodimer-specific ELISA; conditional Bmp10-KO mouse; ALK1-transfected 3T3 reporter cell assay; endothelial pSmad1-5 assay; affinity chromatography of human plasma The Journal of biological chemistry High 29789425
2007 BMP10 localizes on the cell surface and at the stretch-sensing Z-disc of cardiomyocytes and interacts with titin-cap (Tcap) at this location. A rare human BMP10 variant (Thr326Ile) shows decreased binding to Tcap and increased extracellular secretion, and conditioned medium from Thr326Ile-expressing cells shows enhanced hypertrophic effect on rat neonatal cardiomyocytes compared to wild-type BMP10. Co-immunoprecipitation; subcellular localization by immunofluorescence; binding assay with variant; neonatal cardiomyocyte hypertrophy assay with conditioned medium American journal of physiology. Heart and circulatory physiology Medium 17921333
2019 BMP10 activates both the canonical SMAD-mediated signaling pathway and, unexpectedly, the STAT3-mediated signaling pathway in cardiomyocytes both in vivo and in vitro. BMP10 cardioprotective function (reducing apoptosis and fibrosis in response to isoproterenol) is attributable to dual activation of SMAD and STAT3 pathways. Intraperitoneal recombinant human BMP10 protects hearts from injury in mice. Transgenic and conditional BMP10 overexpression mice; isoproterenol cardiac injury model; gene profiling and biochemical pathway analysis; recombinant BMP10 administration; in vivo and in vitro SMAD and STAT3 pathway activation assays The Journal of biological chemistry High 31712309
2020 Crystal structure of the BMP10:ALK1 complex (2.3 Å) reveals a tripartite recognition mechanism defining BMP9 and BMP10 specificity for ALK1. Introduction of BMP10-specific residues into BMP9 yields BMP10-like ligands with diminished C2C12 signaling activity, validating the structural mechanism. Structural analysis predicts (and experiments confirm) that crossveinless 2 is not an inhibitor of BMP9. The prodomain-bound BMP9:ALK1 structure (3.3 Å) was also resolved. X-ray crystallography; mutagenesis; C2C12 cell signaling assay; crossveinless 2 inhibition assay Nature communications High 32238803
2022 Crystal structures of binary and ternary BMPRII extracellular domain complexes with BMP10 (ensemble of seven different BMP10:BMPRII 1:1 complexes) reveal that BMPRII binds BMP10 at the knuckle epitope via A-loop and β4 strand BMPRII-specific interactions. The BMPRII binding surface on BMP10 is dynamic; affinity is weaker in the ternary complex than in the binary complex. Hydrophobic core and A-loop interactions are important for BMPRII-mediated signaling. X-ray crystallography; structure-function analysis; multiple crystal forms Nature communications High 35504921
2020 BMP10 (along with BMP9) signals through ALK1 as the type I receptor and ACTR-IIA and BMPR-II as type II receptors to repress basal CCL2 expression and release from human pulmonary artery and aortic endothelial cells. This repression is Smad4-dependent. Smad1/5 contributes only at concentrations similar to circulating BMP9 levels. siRNA knockdown of ALK1, ACTR-IIA, BMPR-II, Smad4, Smad1/5; ELISA for CCL2; endothelial cell culture Journal of cell science Medium 32576665
2020 BMP9 and BMP10 act directly on vascular smooth muscle cells (VSMCs) to induce and maintain their contractile state via ALK1 and downstream SMAD7. Combined genetic inactivation of Bmp9 and Bmp10 (in right atrium) causes dramatic reduction of VSMC contractility and decreased systemic and pulmonary blood pressure. Overexpression of Bmp10 in endothelial cells enhances contractile VSMC formation and increases blood pressure. ALK1 deletion in VSMCs recapitulates the Bmp9/10 phenotype in pulmonary but not aortic/coronary arteries. Cell type-specific conditional knockout and overexpression transgenic mice; blood pressure measurement; morphometric and expression analysis; isolated pulmonary VSMC phenotypic assays; smFISH Circulation High 33334130
2020 BMP10 signaling promotes specification of endocardial cells from human pluripotent stem cell-derived cardiovascular progenitors. BMP10 is required for development of an hPSC-derived endothelial population with endocardial characteristics including expression of endocardium-specific genes, capacity to induce trabecular fate in cardiomyocytes, and ability to undergo endothelial-to-mesenchymal transition. hPSC differentiation; signaling pathway inhibition/activation; gene expression analysis; co-culture functional assays; endothelial-to-mesenchymal transition assay Cell stem cell Medium 33142114
2017 BMP9 and BMP10 synergize with TNF-α to increase monocyte recruitment to vascular endothelium via upregulation of E-selectin, VCAM-1, and ICAM-1. The effect is mediated mainly via the ALK2 type I receptor (for E-selectin), and both ALK1 and ALK2 (for VCAM-1 and ICAM-1), with BMPR-II and ACTR-IIA as type II receptors, and downstream Smad1/5. LDN193189 (ALK2 inhibitor) blocks monocyte recruitment. siRNA knockdown of BMP type I and II receptors and Smads; in vitro flow adhesion assay; surface adhesion molecule expression by flow cytometry; pharmacological inhibition with LDN193189 The Journal of biological chemistry Medium 28646109
2015 BMP9 and BMP10 are required for proper closure of the ductus arteriosus (DA). Bmp9 knockout leads to imperfect DA closure, and combined neutralization of BMP10 in Bmp9-KO pups causes reopening of the DA. This effect is associated with a defect in intimal cell differentiation (endothelial to mesenchymal transition) and lack of ECM deposition, as shown by electron microscopy and immunofluorescence. Bmp9 knockout mice; anti-BMP10 neutralizing antibody administration; transmission electron microscopy; immunofluorescence; gene expression analysis Proceedings of the National Academy of Sciences of the United States of America Medium 26056270
2019 In zebrafish, combined loss of bmp10 and bmp10-like (duplicate paralogs) causes embryonic lethal cranial arteriovenous malformations indistinguishable from acvrl1 mutants. bmp10 single mutants develop post-embryonic vascular defects in skin and liver, heart dysmorphology, and premature death correlated with increased cardiac output, establishing Bmp10 as a non-redundant Alk1 ligand in the juvenile-to-adult period. Zebrafish loss-of-function mutants for bmp9, bmp10, bmp10-like singly and in combination; phenotype analysis of vascular and cardiac structures Angiogenesis High 31828546
2022 BMP10, but not BMP9, is indispensable for arteriovenous network formation. Bmp10-inducible KO mice develop AVMs in retina, postnatal brain, and adult wounded skin, while Bmp9-KO does not show noticeable vascular defects. Administration of BMP10 protein (but not BMP9 protein) prevents retinal AVM in Bmp9/10-dKO and endothelial-specific Eng-iKO mice. Bmp10 deficiency results in increased endothelial cell proliferation and size in AVM vessels. Conditional inducible Bmp10-KO mice; Bmp9-KO; double KO; retinal AVM analysis; recombinant BMP10 and BMP9 rescue experiments; endothelial cell quantification Angiogenesis High 36348215
2025 Proprotein convertase (PPC) processing of BMP-10 is required for bioactivity. Unprocessed BMP-10 adopts a latent wide-angle conformation; processing converts it to a bioactive complex (CPLX) that can adopt a V-shape with tighter angle. Only processed BMP-10 shows high potency in HUVEC and C2C12 cells and robust binding to immobilized BMP receptors. The N-terminal region of the BMP-10 prodomain is alpha-helical and essential for efficient complexation with the growth factor domain. Only processed BMP-10 CPLX interacts with fibrillin-1 N-terminal region, causing fibrillin-1 to adopt a closed ring-shaped conformation. Molecular dynamics simulations; negative staining transmission electron microscopy; circular dichroism; binding assays with BMP receptors; cell-based activity assays (HUVEC, C2C12); fibrillin-1 interaction and TEM analysis FASEB journal High 39921464
2024 BMP10 is produced by hepatic stellate cells (HSCs) in the liver. GDF2/BMP10 secreted by HSCs promote differentiation and identity maintenance of Kupffer cells (KCs) and liver endothelial cells (ECs) via ALK1 (expressed on KCs and ECs). Deletion of Gdf2 and Bmp10 in HSCs upregulates Pdgfb in KCs and ECs, leading to HSC activation and liver fibrosis. Loss of GDF2/BMP10 from HSCs reduces angiocrine factors (BMP2, BMP6, Wnt2, Rspo3) in ECs, causing liver iron overload and disruption of hepatocyte metabolic zonation. Conditional deletion of Gdf2 and Bmp10 in different liver cell types; ALK1 reporter mice; cell-type specific phenotype analysis; gene expression analysis eLife High 39453386
2019 Cytoplasmic BMP10 interacts with both receptor protein tyrosine phosphatase sigma (PTPRS) and STAT3 in hepatocellular carcinoma cells, facilitating dephosphorylation of STAT3 by PTPRS, thereby suppressing tumor cell growth. Co-immunoprecipitation; in vitro and in vivo proliferation assays; loss-of-function experiments; phospho-STAT3 analysis Oncogene Medium 31417183
2013 BMP10 is a potent inducer of trophoblast differentiation in human embryonic and induced pluripotent stem cells, acting via SMAD1/5/8 (canonical) and MAPK p38 (non-canonical) signaling pathways. BMP10 is resistant to NOGGIN-induced inhibition, which contributes to its superior potency compared to BMP4 for trophoblast induction. hESC and hiPSC differentiation assays; BMP receptor expression profiling; signaling pathway analysis (Smad1/5/8, MAPK p38); NOGGIN inhibition experiment; target gene expression Biomaterials Medium 24070570
2024 BMP10 stimulation of endothelial cells activates a non-canonical transcriptional SMAD-dependent MAPK pathway (MEKK4/P38) involving GADD45β. Activated P38 phosphorylates HSP27 and Eps15, and regulates expression of E-selectin, hyaluronan synthase 2, and COX2. BMP10 also induces phosphorylation of ERG and CDK4/6 pathway proteins, and causes G1 cell cycle arrest with inhibition of E2F2, cyclinD1, and cyclinA1 mRNA. Large-scale phosphoproteomics; western blot validation; RT-qPCR; flow cytometry cell cycle analysis; siRNA validation Cell communication and signaling : CCS Medium 38439036
2021 Gsα regulates BMP10 expression through CREB1 binding to the Bmp10 promoter. Cardiac-specific Gsα disruption decreases CREB1 expression and inhibits BMP10-mediated signaling, causing cardiac dysfunction and severe remodeling. Tamoxifen-inducible cardiac-specific Gsα knockout mice; CREB1 expression and promoter binding analysis; cardiac function assessment; signaling pathway analysis Cell death discovery Medium 34907172
2024 BMP10 activates spinal astrocytes via the ALK2/Smad1/5/8 signaling axis. In a neuropathic pain model, BMP10 is elevated in ipsilateral spinal dorsal horn astrocytes. BMP10 siRNA reduces pain hypersensitivity and astrocytic activation; exogenous BMP10 peptide evokes pain hypersensitivity and astrocytic activation, reversed by ALK2 inhibition. Smad1 siRNA inhibits BMP10-induced astrocytic activation and hypersensitivity. Spared nerve injury mouse model; intrathecal siRNA and peptide administration; western blot; immunofluorescence; behavioral assays; LPS-stimulated astrocyte model with Smad1 siRNA Frontiers in pharmacology Medium 39188955
2021 BMP10 stimulates myogenic differentiation, glucose uptake, and lipid catabolism in C2C12 myoblasts via the Smad1/5/8 signaling pathway. BMP10 silencing prevents these processes, while exogenous BMP10 stimulates mitochondrial biogenesis and thermogenesis. Bmp10 siRNA knockdown; exogenous BMP10 treatment; Smad1/5/8 pathway inhibition/activation; differentiation and metabolic assays in C2C12 cells Molecular and cellular biochemistry Low 33517521
2024 bmp10 deficiency in zebrafish causes cardiac iron deficiency that progresses to iron overload due to dysregulation of the hepcidin/ferroportin axis in cardiac cells, leading to ferroptosis and heart failure. Early iron supplementation rescues erythropoiesis in bmp10 mutants; iron chelation alleviates cardiac hypertrophy. HIF1α-driven hypoxic signaling and IL6/p-STAT3 inflammatory pathways are critical for regulating cardiac iron metabolism downstream of bmp10. Zebrafish bmp10 loss-of-function mutants; iron supplementation and chelation rescue experiments; hepcidin/ferroportin expression analysis; HIF1α and IL6/STAT3 pathway analysis Journal of genetics and genomics Medium 39414074
2025 High-rate atrial pacing (optogenetic, 3–5 Hz) increases BMP10 release from atrial (but not ventricular) human iPSC-derived engineered heart tissue approximately 3-fold, with a latency of at least 24 hours. BMP10 exposure to ventricular EHTs induces upregulation of TGFβ pathway transcripts, increases expression of genes related to AF and heart failure (PITX2, NPPB), and increases relative contraction times, establishing BMP10 as a potential mediator of AF-induced ventricular remodeling. Human iPSC-derived atrial and ventricular engineered heart tissue; optogenetic pacing; BMP10 ELISA; transcriptomic analysis; functional contractility assay Circulation. Arrhythmia and electrophysiology Medium 41090224
2011 BMP10 is expressed in blood cells during embryonic development (in situ hybridization), and overexpression of BMP10 in transgenic mice enhances ATF3 expression, suggesting ATF3 is a downstream target regulated via Smad-dependent pathway. NOTE: This paper is largely hypothesis/speculation; the only direct experimental finding is the in situ expression data and the transgenic overexpression showing increased ATF3. In situ hybridization; BMP10 overexpression transgenic mouse; ATF3 expression analysis Medical hypotheses Low 21345597
2023 A BMP10 missense variant (Gln56*) found in a family with autosomal-dominant dilated cardiomyopathy loses the ability to transactivate target genes NKX2.5 and TBX20 in a dual-luciferase reporter assay, supporting BMP10 haploinsufficiency as a mechanism for DCM. Whole-exome sequencing; Sanger sequencing; dual-luciferase reporter assay for NKX2.5 and TBX20 transactivation Diagnostics (Basel, Switzerland) Low 36673052
2024 A BMP10 nonsense variant (Glu83*) found in a family with patent ductus arteriosus lacks transactivation activity on TBX20 and NKX2.5 target genes in a dual-luciferase reporter assay. Whole-exome sequencing; dual-luciferase reporter assay for TBX20 and NKX2.5 transactivation in HeLa cells American journal of translational research Low 38322548
2025 BMP-9 and BMP-10 are secreted as a mixture of disulfide-linked dimers and monomers. Monomers are secreted in cysteinylated form and have reduced signaling potency compared to disulfide-linked dimers. Geometric strain across the interchain disulfide (syn-periplanar conformation, shown by X-ray crystallography) is responsible for infrequent interchain disulfide bond formation. Interchain disulfide bond formation occurs less in BMP-9 than BMP-10, and this difference can be reversed by swapping residues near the interchain disulfide. X-ray crystallography (BMP-9 homodimer interchain disulfide structure); analytical ultracentrifugation; protein secretion assays; signaling potency comparison; residue-swapping mutagenesis Journal of molecular biology High 39793884
2024 Loss-of-function GDF2 variants impair secretion of both BMP9 and BMP10 (detected by ELISA and Western blot), suggesting a dominant-negative mechanism where BMP9 loss affects BMP10 circulating levels. BMP10 variant loss of function is mostly due to altered processing (folding/stability defects) as shown by expression studies. Functional reporter assay (C2C12 BRE-luciferase); ELISA; Western blot; expression and secretion analysis of GDF2 and BMP10 variants Circulation. Genomic and precision medicine Medium 42261662

Source papers

Stage 0 corpus · 69 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Identification of BMP9 and BMP10 as functional activators of the orphan activin receptor-like kinase 1 (ALK1) in endothelial cells. Blood 578 17068149
2004 BMP10 is essential for maintaining cardiac growth during murine cardiogenesis. Development (Cambridge, England) 407 15073151
2012 BMP9 and BMP10 are critical for postnatal retinal vascular remodeling. Blood 205 22566602
1999 Heart specific expression of mouse BMP-10 a novel member of the TGF-beta superfamily. Mechanisms of development 134 10072785
2013 Context-dependent signaling defines roles of BMP9 and BMP10 in embryonic and postnatal development. Proceedings of the National Academy of Sciences of the United States of America 105 23812757
2020 Characterization of GDF2 Mutations and Levels of BMP9 and BMP10 in Pulmonary Arterial Hypertension. American journal of respiratory and critical care medicine 103 31661308
2015 Emerging roles of BMP9 and BMP10 in hereditary hemorrhagic telangiectasia. Frontiers in genetics 98 25620979
2018 A heterodimer formed by bone morphogenetic protein 9 (BMP9) and BMP10 provides most BMP biological activity in plasma. The Journal of biological chemistry 93 29789425
2012 Myocardin regulates BMP10 expression and is required for heart development. The Journal of clinical investigation 85 22996691
2013 Circulating Bmp10 acts through endothelial Alk1 to mediate flow-dependent arterial quiescence. Development (Cambridge, England) 80 23863480
2020 Reduced left atrial cardiomyocyte PITX2 and elevated circulating BMP10 predict atrial fibrillation after ablation. JCI insight 79 32814717
2020 Molecular basis of ALK1-mediated signalling by BMP9/BMP10 and their prodomain-bound forms. Nature communications 68 32238803
2020 BMP10 Signaling Promotes the Development of Endocardial Cells from Human Pluripotent Stem Cell-Derived Cardiovascular Progenitors. Cell stem cell 68 33142114
2019 BMP10-mediated ALK1 signaling is continuously required for vascular development and maintenance. Angiogenesis 67 31828546
2020 BMP9 and BMP10 Act Directly on Vascular Smooth Muscle Cells for Generation and Maintenance of the Contractile State. Circulation 63 33334130
2021 BMP9 and BMP10: Two close vascular quiescence partners that stand out. Developmental dynamics : an official publication of the American Association of Anatomists 62 34240497
2022 Different cardiovascular and pulmonary phenotypes for single- and double-knock-out mice deficient in BMP9 and BMP10. Cardiovascular research 60 34086873
2016 A mouse model of hereditary hemorrhagic telangiectasia generated by transmammary-delivered immunoblocking of BMP9 and BMP10. Scientific reports 56 27874028
2015 BMP9 and BMP10 are necessary for proper closure of the ductus arteriosus. Proceedings of the National Academy of Sciences of the United States of America 54 26056270
2017 Bone morphogenetic protein 9 (BMP9) and BMP10 enhance tumor necrosis factor-α-induced monocyte recruitment to the vascular endothelium mainly via activin receptor-like kinase 2. The Journal of biological chemistry 50 28646109
2020 Reduced circulating BMP10 and BMP9 and elevated endoglin are associated with disease severity, decompensation and pulmonary vascular syndromes in patients with cirrhosis. EBioMedicine 47 32454407
2016 Regulation of the ALK1 ligands, BMP9 and BMP10. Biochemical Society transactions 47 27528761
2019 BMP10 preserves cardiac function through its dual activation of SMAD-mediated and STAT3-mediated pathways. The Journal of biological chemistry 46 31712309
2018 BMP9, but not BMP10, acts as a quiescence factor on tumor growth, vessel normalization and metastasis in a mouse model of breast cancer. Journal of experimental & clinical cancer research : CR 40 30165893
2007 Interaction of BMP10 with Tcap may modulate the course of hypertensive cardiac hypertrophy. American journal of physiology. Heart and circulatory physiology 38 17921333
2021 Homozygous GDF2 nonsense mutations result in a loss of circulating BMP9 and BMP10 and are associated with either PAH or an "HHT-like" syndrome in children. Molecular genetics & genomic medicine 35 33834622
2013 BMP10 as a potent inducer of trophoblast differentiation in human embryonic and induced pluripotent stem cells. Biomaterials 34 24070570
2008 Cell therapy using articular chondrocytes overexpressing BMP-7 or BMP-10 in a rabbit disc organ culture model. Spine 32 18404100
2022 BMP10 functions independently from BMP9 for the development of a proper arteriovenous network. Angiogenesis 28 36348215
2022 Astragalus polysaccharides alleviates cardiac hypertrophy in diabetic cardiomyopathy via inhibiting the BMP10-mediated signaling pathway. Phytomedicine : international journal of phytotherapy and phytopharmacology 28 36610158
2020 Endothelial protective factors BMP9 and BMP10 inhibit CCL2 release by human vascular endothelial cells. Journal of cell science 24 32576665
2024 Circulating BMP10 Levels Associate With Late Postoperative Atrial Fibrillation and Left Atrial Endomysial Fibrosis. JACC. Clinical electrophysiology 20 38639699
2004 Highly restricted BMP10 expression in the trabeculating myocardium of the chick embryo. Development genes and evolution 18 14722768
2024 Impact of heterozygous ALK1 mutations on the transcriptomic response to BMP9 and BMP10 in endothelial cells from hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension donors. Angiogenesis 16 38294582
2023 Identification of BMP10 as a Novel Gene Contributing to Dilated Cardiomyopathy. Diagnostics (Basel, Switzerland) 16 36673052
2015 BMP10 inhibited the growth and migration of gastric cancer cells. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 16 26419594
2024 Large-scale phosphoproteomics reveals activation of the MAPK/GADD45β/P38 axis and cell cycle inhibition in response to BMP9 and BMP10 stimulation in endothelial cells. Cell communication and signaling : CCS 14 38439036
2024 GDF2 and BMP10 coordinate liver cellular crosstalk to maintain liver health. eLife 13 39453386
2023 GATA6 coordinates cross-talk between BMP10 and oxidative stress axis in pulmonary arterial hypertension. Scientific reports 13 37087509
2022 Crystal structures of BMPRII extracellular domain in binary and ternary receptor complexes with BMP10. Nature communications 13 35504921
2019 BMP10 suppresses hepatocellular carcinoma progression via PTPRS-STAT3 axis. Oncogene 13 31417183
2024 Repeated Measurement of the Novel Atrial Biomarker BMP10 (Bone Morphogenetic Protein 10) Refines Risk Stratification in Anticoagulated Patients With Atrial Fibrillation: Insights From the ARISTOTLE Trial. Journal of the American Heart Association 12 38529655
2013 Expression of bone morphogenetic protein-10 (BMP10) in human urothelial cancer of the bladder and its effects on the aggressiveness of bladder cancer cells in vitro. Anticancer research 12 23645739
2021 Gsα deficiency facilitates cardiac remodeling via CREB/ Bmp10-mediated signaling. Cell death discovery 10 34907172
2014 Expression analysis of BMP2, BMP5, BMP10 in human colon tissues from Hirschsprung disease patients. International journal of clinical and experimental pathology 10 24551273
2012 The cell-specific upregulation of bone morphogenetic protein-10 (BMP-10) in a model of rat cortical brain injury. Journal of molecular histology 9 22797972
2022 A rare homozygous missense GDF2 (BMP9) mutation causing PAH in siblings: Does BMP10 status contribute? American journal of medical genetics. Part A 7 36259599
2019 Effect of miR-181a-3p on osteogenic differentiation of human bone marrow-derived mesenchymal stem cells by targeting BMP10. Artificial cells, nanomedicine, and biotechnology 7 31713441
2025 Prodomain processing controls BMP-10 bioactivity and targeting to fibrillin-1 in latent conformation. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 6 39921464
2021 Assessment of plasma BMP-2, BMP-7, BMP-10, vitamin D, and TGF β1 in simple fractures among Sudanese patients. PloS one 6 33606840
2011 The potential role of ATF3 on immune response is regulated by BMP10 through Smad dependent pathway. Medical hypotheses 6 21345597
2024 Discovery of BMP10 as a new gene underpinning congenital heart defects. American journal of translational research 4 38322548
2024 BMP10 accelerated spinal astrocytic activation in neuropathic pain via ALK2/smad1/5/8 signaling. Frontiers in pharmacology 4 39188955
2024 bmp10 maintains cardiac function by regulating iron homeostasis. Journal of genetics and genomics = Yi chuan xue bao 4 39414074
2024 BMP10 Knockdown Modulates Endothelial Cell Immunoreactivity by Inhibiting the HIF-1α Pathway in the Sepsis-Induced Myocardial Injury. Journal of cellular and molecular medicine 3 39611400
2022 BMP10 expression in the adult rat central nervous system. Journal of chemical neuroanatomy 3 35182716
2025 High Rate Triggers Increased Atrial Release of BMP10, A Biomarker for Atrial Fibrillation and Stroke, and BMP10 Affects Ventricular Cardiomyocytes. Circulation. Arrhythmia and electrophysiology 2 41090224
2021 BMP10 positively regulates myogenic differentiation in C2C12 myoblasts via the Smad 1/5/8 signaling pathway. Molecular and cellular biochemistry 2 33517521
2025 Molecular Basis of Interchain Disulfide Bond Formation in BMP-9 and BMP-10. Journal of molecular biology 1 39793884
2025 Coordinated expression of BMP10/ALK1/endoglin-proteins that drive embryonic cardiac and vascular morphogenesis-in patients with heart failure: The EMPEROR Program. European journal of heart failure 1 40660089
2025 BMP10 attenuates age-related atrial fibrillation susceptibility through improving mitochondrial function in atrial cardiomyocytes. Archives of gerontology and geriatrics 1 40896981
2026 Exosomal Rspondin3 serves as a master regulator of immunometabolic repair in sepsis: synergistic activation of macrophage M2 polarization and endothelial BMP10 signaling. International immunopharmacology 0 41839470
2026 Hepatic Stellate Cell-Specific METTL3 Deficiency Promotes Hepatocellular Carcinoma Progression via BMP10-SMAD1/5/8 Signaling. Cancer research communications 0 42030359
2026 Phlorizin activates BMP10 to attenuate atherosclerosis by inhibiting vascular endothelial senescence and inflammation in Apoe-/- mice. International immunopharmacology 0 42202394
2026 Hypothermic Treatment Alleviates Myocardial Hypertrophy in bmp10-/- Zebrafish. Frontiers in bioscience (Landmark edition) 0 42216530
2026 Functional and Molecular Characterization of Novel GDF2 (BMP9) and BMP10 Variants From the French PAH and HHT Cohorts. Circulation. Genomic and precision medicine 0 42261662
2025 BMP10 in Cardiovascular Disease: From Pathogenesis to Therapeutic Strategies. Frontiers in bioscience (Landmark edition) 0 40765332
2024 Molecular basis of interchain disulfide-bond formation in BMP-9 and BMP-10. bioRxiv : the preprint server for biology 0 39464140
2022 Generation of a human embryonic stem cell line targeted homozygous deletion of BMP10 (WAe007-A-2) by CRISPR/Cas9-dgRNA. Stem cell research 0 36257094

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