Affinage

BMP7

Bone morphogenetic protein 7 · UniProt P18075

Length
431 aa
Mass
49.3 kDa
Annotated
2026-04-28
100 papers in source corpus 40 papers cited in narrative 40 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMP7 is a secreted TGF-β superfamily ligand that functions predominantly as a heterodimer with BMP2 or BMP4 in vivo to regulate embryonic patterning, organogenesis, tissue homeostasis, and regeneration across multiple organ systems (PMID:31566563, PMID:10662635). BMP7 signals through type I receptors ALK2 and ALK3 and type II receptors ActRIIA, ActRIIB, and BMPRII to activate canonical SMAD1/5/8-dependent transcription—potentiated by UBE2O-mediated monoubiquitination of inhibitory SMAD6—as well as non-canonical TAK1–JNK–AP-1, p38 MAPK, and PI3K–Akt–mTOR pathways, with pathway selection determining context-specific outcomes including nephron progenitor self-renewal, Langerhans cell differentiation, brown adipogenesis, cardiomyocyte proliferation, and macrophage M2 polarization (PMID:26634297, PMID:24190429, PMID:38678558, PMID:23455153, PMID:24376781). A central homeostatic function of BMP7 is antagonism of TGF-β/SMAD2/3-driven fibrosis and epithelial-to-mesenchymal transition in kidney, liver, and eye, achieved by maintaining SMAD1/5/8 signaling and inducing PTEN to suppress Akt activation (PMID:28923783, PMID:17127702, PMID:30383450). BMP7-null mice die postnatally with kidney agenesis, skeletal patterning defects, and eye abnormalities, establishing BMP7 as essential for kidney, skeletal, and eye development (PMID:9013703).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1990 High

    Establishing the molecular identity of BMP7 as a TGF-β superfamily member resolved what the osteogenic protein OP-1 encoded and placed it within a conserved signaling ligand family.

    Evidence cDNA cloning and sequence analysis from human cDNA library with synthetic consensus probe

    PMID:2357959

    Open questions at the time
    • No receptor or downstream signaling pathway identified
    • Protein processing and secretion mechanism unknown
  2. 1997 High

    BMP7-null mice revealed that BMP7 is essential for kidney, skeletal, and eye development, transforming it from an osteogenic factor into a multi-organ developmental signal.

    Evidence Insertional mutagenesis inactivating Bmp7 in mice with phenotypic analysis of homozygous nulls

    PMID:9013703

    Open questions at the time
    • Cell-type-specific contributions of BMP7 within each organ not resolved
    • Redundancy with other BMPs not yet addressed
  3. 2000 High

    Zebrafish genetics established that BMP7 functions primarily as a heterodimer with BMP2b in vivo for dorsoventral patterning, resolving a key question about whether BMP homodimers or heterodimers are the physiologically relevant signaling species.

    Evidence Double-mutant epistasis, mRNA injection rescue, and temperature-sensitive allele analysis in zebrafish

    PMID:10603351 PMID:10662635

    Open questions at the time
    • Heterodimer formation not yet confirmed biochemically in mammals
    • Prodomain role in heterodimer assembly uncharacterized
  4. 2001 High

    Compound knockouts of BMP6/7 and BMP7/8a revealed functional redundancy among BMP subfamily members in cardiac septation and spermatogenesis, clarifying why single knockouts showed limited phenotypes in these tissues.

    Evidence Double-knockout mouse analysis with embryonic cardiac and reproductive phenotyping

    PMID:11437450 PMID:11784057

    Open questions at the time
    • Shared versus distinct receptor usage among redundant BMPs not determined
    • Signaling pathways downstream in cardiac and reproductive tissues not dissected
  5. 2003 High

    Structural determination of the BMP7–ActRII complex revealed a novel mode of cooperative receptor assembly without direct receptor–receptor contacts, establishing the biophysical basis for ligand-mediated receptor oligomerization.

    Evidence Crystal structure of BMP7 bound to ActRII extracellular domain

    PMID:14559178

    Open questions at the time
    • Type I receptor recruitment mechanism not captured structurally
    • Heterodimer–receptor complex structure unavailable
  6. 2006 High

    BMP7 was shown to counteract TGF-β-driven fibrosis in liver by activating SMAD1/5/8 and Id2 while suppressing collagen and myofibroblast markers, establishing the mechanistic basis for BMP7 as an antifibrotic signal.

    Evidence Adenoviral BMP7 expression in hepatic stellate cells plus in vivo rat fibrosis model with Smad phosphorylation and target gene analysis

    PMID:17127702

    Open questions at the time
    • Whether BMP7 antifibrotic effect operates identically across all organs not established
    • Direct transcriptional targets beyond Id2 not identified
  7. 2007 High

    Dissection of BMP7 signaling in podocytes and through endoglin revealed context-dependent Smad selectivity (Smad5 but not Smad1 in podocytes) and modulation by the TGF-β co-receptor endoglin, refining the canonical signaling model.

    Evidence Smad5 knockdown/overexpression in podocytes; endoglin reconstitution in L6E9 cells with reporter assays

    PMID:17376778 PMID:17804487

    Open questions at the time
    • Basis for selective Smad5 versus Smad1 activation unknown
    • Endoglin's role in BMP7 signaling in vivo not validated
  8. 2008 High

    Podocyte-specific BMP7 knockout demonstrated that paracrine BMP7 from podocytes is required for nephron maturation via p38 MAPK and β-catenin rather than canonical SMAD1/5/8, establishing a non-canonical signaling requirement in kidney development.

    Evidence Nphs2-Cre conditional KO with phospho-p38, phospho-Smad, and β-catenin analysis

    PMID:18923055

    Open questions at the time
    • Direct substrate of p38 MAPK in this context not identified
    • How β-catenin degradation is controlled by BMP7-p38 axis unknown
  9. 2009 High

    Identification of PI3K-dependent chemotaxis via ActRIIA/BMPRII and BDNF-MAPK/ERK-dependent BMP7 induction in neurons expanded the signaling repertoire beyond canonical Smad pathways and revealed upstream regulators of BMP7 expression.

    Evidence RNAi of type II receptors plus PI3K inhibitor in chemotaxis assays; BDNF-induced BMP7 expression with MAPK/ERK pathway analysis in embryonic neurons

    PMID:20011660 PMID:20038543

    Open questions at the time
    • Direct PI3K effectors mediating chemotaxis not identified
    • Whether BDNF-BMP7 axis operates broadly or is neuron-specific unclear
  10. 2013 High

    Multiple studies converged to define tissue-specific BMP7 outputs: UBE2O-mediated monoubiquitination of SMAD6 potentiates canonical signaling and adipogenesis; ALK3-dependent signaling drives Langerhans cell differentiation independently of TGF-β1/ALK5; and PI3K-Akt-mTOR promotes M2 macrophage polarization.

    Evidence UBE2O ubiquitination assays with K174 mutagenesis; Bmp7 KO mice and ALK3 blocking for LC differentiation; PI3K inhibitor with monocyte culture

    PMID:23455153 PMID:24190429 PMID:24376781

    Open questions at the time
    • Whether UBE2O-SMAD6 axis is BMP7-specific or general to all BMPs unknown
    • How ALK3 specificity is enforced in LC precursors not determined
  11. 2015 High

    BMP7 was found to promote nephron progenitor self-renewal through TAK1–JNK–JUN/AP-1 driving G1-S progression, and BMP7 homodimer activity was distinguished from heterodimer contributions by demonstrating preferential heterodimer function during mammalian embryogenesis.

    Evidence Conditional Tak1 and Jun KO in cap mesenchyme with cell cycle analysis; knock-in mouse preventing BMP7 precursor processing with compound Bmp2/Bmp4 heterozygotes and endogenous co-IP

    PMID:26634297 PMID:31566563

    Open questions at the time
    • Relative abundance of BMP7 homodimers versus heterodimers in specific tissues unquantified
    • AP-1 target gene specificity beyond Myc and Ccnd1 not defined
  12. 2017 High

    BMP7's antifibrotic mechanism was refined to include PTEN induction suppressing PI3K/Akt, and BMP7 was shown to be required for uterine receptivity and decidualization, extending its homeostatic roles to reproduction.

    Evidence UUO mouse model with PTEN analysis in tubular cells; Pgr-Cre conditional uterine KO with fertility and gene expression analysis

    PMID:28324064 PMID:28923783

    Open questions at the time
    • Transcriptional mechanism of PTEN induction by BMP7 not established
    • Downstream effectors of BMP7 in decidualization beyond Wnt4/Cox2/Bmp2 not mapped
  13. 2024 High

    BMP7 was established as a cardiomyocyte mitogen acting through BMPR1A/ACVR1 and ACVR2A/BMPR2 via SMAD5, ERK, and AKT to promote cardiac regeneration, validated across mouse and zebrafish.

    Evidence Neonatal mouse cardiomyocyte Bmp7 knockdown, adult zebrafish loss-of-function, and in vivo BMP7 administration post-MI with receptor and pathway analysis

    PMID:38678558

    Open questions at the time
    • Whether BMP7 acts as homodimer or heterodimer in cardiac regeneration unknown
    • Long-term functional cardiac recovery not assessed
    • Direct transcriptional targets driving cardiomyocyte cell cycle re-entry not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • The relative contributions of BMP7 homodimers versus BMP2/7 and BMP4/7 heterodimers in each tissue context, the structural basis for heterodimer-specific receptor engagement, and the mechanisms governing pathway selection between canonical SMAD and non-canonical cascades in different cell types remain unresolved.
  • No structure of BMP heterodimer–receptor complex available
  • Quantitative heterodimer versus homodimer ratios in tissues not measured
  • Decision logic for SMAD versus non-canonical pathway selection not defined

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 3 GO:0031012 extracellular matrix 2
Pathway
R-HSA-162582 Signal Transduction 13 R-HSA-1266738 Developmental Biology 9 R-HSA-168256 Immune System 4 R-HSA-1430728 Metabolism 2
Partners
ACVR2AALK3BMP2BMP4BMPR2GREM1SMAD6UBE2O

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 BMP7 (OP-1) encodes a secreted osteogenic protein belonging to the TGF-β superfamily, with amino acid sequence homology to Drosophila DPP and Xenopus Vg-1, and is the human homolog of a major component of bovine osteogenic protein. cDNA cloning, sequence analysis, library screening with synthetic consensus probe The EMBO journal High 2357959
1991 BMP7 (murine OP-1) mRNA is expressed at maximal levels in the kidney, with multiple mRNA species (2.2 kb major, 1.8 and 2.4 kb minor, 4 kb large species possibly representing alternative splices), suggesting the kidney as the main site of OP-1 synthesis. Northern blot hybridization of mouse organ tissues using murine OP-1 cDNA probes Biochemical and biophysical research communications High 1715687
1992 BMP7 maps to human chromosome 20 (syntenic with BMP2), and together with BMP5 and BMP6 forms a BMP subfamily based on high amino acid sequence homology; the Drosophila 60A gene is identified as the dipteran homolog of this subfamily. Human-rodent somatic cell hybrid lines, cDNA probes, chromosomal mapping Genomics High 1427904
1997 BMP7 null mutation in mice causes postnatal lethality with skeletal defects (holes in basisphenoid bone, fused ribs/vertebrae, polydactyly), reduced nephron number, polycystic kidney, lack of retinal pigmentation, and retarded lens development, establishing BMP7 as an essential signaling molecule for skeleton, kidney, and eye development. Insertional mutagenesis (transgene integration inactivating Bmp7 gene), phenotypic analysis of homozygous null mice Experimental cell research High 9013703
1997 BMP7 signals through the BMP2/7 receptor (XALK2) to inhibit neural fate and induce epidermal fate in Xenopus ectoderm; a constitutively active mutant of XALK2 signals ligand-independently to block neuralization and induce epidermis, and a dominant-negative BMP2 ligand causes neuralization. Xenopus overexpression/dominant-negative experiments, receptor isolation and constitutively active mutant generation, dissociated ectoderm assays Developmental biology High 9281341
1998 BMP7 expression in the metanephric mesenchyme is dependent on proteoglycan synthesis (disrupted by sodium chlorate treatment) and on inductive signals likely involving Wnt signaling (mimicked by LiCl), while BMP7 expression in the epithelial components of the kidney is not subject to autoregulation and is independent of cell-cell or cell-ECM interactions with the mesenchyme. Beta-gal reporter allele knock-in at BMP7 locus, recombinant BMP7 treatment of isolated kidney mesenchyme, sodium chlorate treatment, LiCl treatment, heterologous recombination experiments Development (Cambridge, England) High 9693150
2000 Zebrafish Bmp7 (snailhouse) is required for specification of ventral cell fates during dorsoventral patterning; Bmp7 null mutants are strongly dorsalized, identical in phenotype to Bmp2b (swirl) null mutants; Bmp2b and Bmp7 synergize in ventralization through a cell-autonomous mechanism, suggesting Bmp2b/Bmp7 heterodimers act in vivo; Bmp2b/Bmp7 signaling is transduced by Smad5 and antagonized by Chordino. Genetic mapping, allele isolation, mRNA injection rescue, double mutant analysis, temperature-sensitive allele characterization Development (Cambridge, England) High 10603351 10662635
2000 A missense mutation (Val→Gly) in the conserved Bmp7 prodomain (snailhouse ty68 allele) is temperature-sensitive and affects secretion and/or stability of secreted mature Bmp7 after processing, demonstrating that the prodomain is essential for normal BMP7 function. Molecular characterization of temperature-sensitive allele, secretion/stability assays Development (Cambridge, England) High 10603351
2001 Bmp6 and Bmp7 cooperate to promote formation of the outflow tract endocardial cushions and cardiac septation during mouse heart development; neither Bmp6 nor Bmp7 alone is required, but double mutants show marked delay in cushion formation, valve morphogenesis defects, and embryonic lethality from cardiac insufficiency. Single and double knockout mouse analysis, embryonic phenotyping Developmental biology High 11437450
2001 Bmp7 plays a role in maintenance of spermatogenesis and epididymal function, redundant with Bmp8a; removal of one allele of Bmp7 exacerbates the Bmp8a null phenotype, suggesting BMP8a and BMP7 signal through the same or similar receptors in these tissues. Bmp7/Bmp8a double mutant analysis, genetic epistasis Developmental biology Medium 11784057
2002 BMP-7 activates Smad1 phosphorylation (but not Smad2) in corneal fibroblasts and does not induce myofibroblast differentiation (alpha-smooth muscle actin, fibronectin), in contrast to activin A which activates Smad2/3 and promotes myofibroblast differentiation. Western blot for Smad phosphorylation, antisense Smad2/3 transfection, RT-PCR, marker protein quantification Investigative ophthalmology & visual science Medium 11773015
2003 The structure of BMP7 bound to the extracellular domain of activin type II receptor (ActRII) reveals a new mode of ligand-mediated cooperative receptor assembly without receptor-receptor contacts. Crystal structure determination (structural analysis reviewed) Trends in biochemical sciences High 14559178
2003 Loss of both Hoxa13 function and Bmp7 expression (together with Fgf8) in the urethral plate epithelium causes hypospadias in mice; Bmp7 is essential for apoptosis in the distal urethra, and reduced Bmp7 expression leads to closure defects. Hoxa13 knockout mouse analysis, in situ hybridization, in vitro growth factor supplementation Development (Cambridge, England) High 12783783
2004 BMP-7 stimulates formation of hyaluronan (HA) cable-like structures on proximal tubular cells (HK-2), increases CD44-dependent monocyte binding, upregulates HAS2 mRNA expression, and decreases expression of Hyal1 and Hyal2 hyaluronidases, modulating proximal tubular cell-monocyte interaction. Cell culture, radiolabeled cell binding assay, RT-PCR, HA cable structure characterization Journal of the American Society of Nephrology : JASN Medium 15100360
2006 BMP-7 suppresses liver fibrosis by antagonizing TGFβ-induced collagen 1A2 mRNA and smooth muscle alpha-actin expression in hepatic stellate cells via Smad1/5/8 phosphorylation, and triggers Id2 mRNA expression; Smad1 and Id2 overexpression increases endogenous BMP-7 expression in LX-2 cells. Adenoviral BMP7 expression in primary rat stellate cells and LX-2, quantitative RT-PCR, in vivo rat fibrosis model (thioacetamide), hydroxyproline content, Smad phosphorylation assays Gut High 17127702
2006 Genetic analysis in mice shows BMP2 and BMP4 (but not BMP7) are required for osteogenesis in the limb; a threshold level of BMP signaling including BMP2/BMP4 is required for chondrogenic condensation onset, but subsequent chondrogenic differentiation proceeds normally even without BMP2 and BMP7. Conditional knockout mice (limb bud mesenchyme-specific), multiple BMP compound mutants, skeletal analysis PLoS genetics High 17194222
2007 Endoglin (CD105) differentially modulates BMP7 and TGFβ1 signaling: endoglin overexpression enhances the BMP7/Smad1/Smad5 pathway while inhibiting TGFβ1-induced ALK-5/Smad3 signaling; BMP7 exclusively activates Smad1/Smad5 leading to prolonged Id1 expression, while BMP7 antagonizes TGFβ1-induced collagen I expression via the ALK-5/Smad3 pathway. Transient transfection of endoglin in endoglin-deficient L6E9 cells, reporter gene assays (CAGA12-MLP-Luc), Western blot for Smad phosphorylation, target gene expression The Journal of biological chemistry High 17376778
2007 BMP7 is a differentiation and survival factor for podocytes that activates Smad5 (but not Smad1) and raises p38 phosphorylation; Smad5 is required and sufficient for BMP7-mediated protection against high glucose- and TGFβ-induced apoptosis in murine podocytes. High glucose treatment of podocytes, BMP7 treatment, Smad5 knockdown and forced expression, caspase-3 activity, apoptosis assays, Western blot American journal of physiology. Renal physiology High 17804487
2008 Podocyte-derived BMP7 is required for nephron maturation: podocyte-specific BMP7 knockout leads to hypoplastic kidneys with reduced proximal tubule number and impaired cellular proliferation; the mechanism involves decreased phosphorylated p38 MAPK and reduced beta-catenin (targeted for degradation) rather than altered Smad1/5/8 phosphorylation. Podocyte-specific conditional KO (Nphs2-Cre), immunostaining, phospho-Smad and phospho-p38 MAPK analysis, beta-catenin localization Journal of the American Society of Nephrology : JASN High 18923055
2008 HDAC5 selectively represses BMP7 expression; ischemia-induced downregulation of HDAC5 in proximal tubular cells leads to histone re-acetylation and induction of BMP7 expression during the regenerative response to renal ischemia. HDAC5 RNAi knockdown, ischemia/reperfusion mouse model, histone acetylation assays, BMP7 expression measurement Journal of the American Society of Nephrology : JASN High 18322163
2009 BMP7-evoked chemotaxis of monocytic cells requires the coordinated activity of ActRIIA and BMPRII (but not ActRIIB) type II BMP receptors, and operates through PI3K-dependent signaling rather than canonical Smad4-dependent transcriptional signaling. RNAi knockdown of individual type II receptor subunits, PI3K inhibitor (LY-294002), chemotaxis assays PloS one High 20011660
2009 BMP7 treatment after spinal cord injury activates the p38 MAPK pro-survival pathway and increases NMDAR-1 levels, resulting in neuronal sparing; BMP7 is also neuroprotective against glutamate-mediated excitotoxicity in cortical neurons. Rat cervical SCI model, BMP7 treatment, Western blot for MAPK-38 and NMDAR-1, histological neuronal count, cortical neuron glutamate toxicity assay Neuroscience letters Medium 19765637
2009 Trps1 functions downstream of Bmp7 during kidney development: Bmp7-deficient kidneys show virtually absent Trps1 expression; Bmp7 induces Trps1 and E-cadherin and downregulates vimentin in cultured metanephric mesenchymal cells; knockdown of Trps1 inhibits Bmp7-induced mesenchymal-to-epithelial transition. Trps1 knockout mice, Bmp7 knockout comparison, cultured metanephric mesenchyme, siRNA knockdown, in situ hybridization Journal of the American Society of Nephrology : JASN High 19820125
2009 BDNF induces BMP7 expression in embryonic neurons by activating MAPK/ERK signaling and through negative regulation of p53/p73 function; intraventricular BMP7 induces premature radial glia differentiation into glial precursors/astrocytes and impairs neuronal migration by terminating radial glia scaffolding support. Intraventricular BMP7 injection in mouse embryos, MAPK/ERK pathway analysis, p53/p73 manipulation, immunohistochemistry for glial markers Cerebral cortex (New York, N.Y. : 1991) Medium 20038543
2013 UBE2O (E2-230K) monoubiquitinates SMAD6 at lysine 174 (requiring cysteine 885 of UBE2O for catalytic activity); this monoubiquitination impairs SMAD6's inhibitory binding to the BMP type I receptor, thereby potentiating BMP7-induced SMAD1 phosphorylation and transcriptional responses; UBE2O and SMAD6 cooperate in BMP7-induced adipogenesis. Whole proteomic interaction screen, ubiquitination assay, site-directed mutagenesis (K174 and C885), SMAD1 phosphorylation assay, receptor binding assay, adipogenesis assay The EMBO journal High 23455153
2013 BMP-7 polarizes monocytes into M2 macrophages through the SMAD-PI3K-Akt-mTOR pathway: BMP-7 increases p-SMAD1/5/8 and p-PI3K, activating downstream p-Akt and p-mTOR, while inhibiting p-PTEN; PI3K inhibition (LY-294002) reduces BMP-7-induced IL-10 and arginase-1 upregulation. Monocyte culture, BMP-7 treatment with follistatin inhibition, PI3K inhibitor, Western blot for pathway components, cytokine ELISA PloS one Medium 24376781
2013 BMP7 induces Langerhans cell (LC) differentiation and proliferation by activating the BMP type I receptor ALK3, independent of canonical TGF-β1-ALK5 signaling; selective ALK3 signaling by BMP7 promotes high LC yields, whereas TGF-β1-driven LC generation also co-induces ALK5 which diminishes output; Bmp7-deficient mice exhibit substantially reduced LC numbers. Bmp7 knockout mice, ALK3/ALK5 receptor blocking, in vitro LC differentiation from CD34+ progenitors and monocytes, immunostaining The Journal of experimental medicine High 24190429
2013 BMP7 promotes brown adipose tissue (BAT) differentiation and reduces white adipose tissue (WAT) mass, and these effects require sympathetic activation of BAT (only at subthermoneutral temperature of 21°C, not at thermoneutral 28°C); BMP7 also induces browning of WAT independent of environmental temperature. Subcutaneous osmotic minipump BMP7 delivery in mice at 21°C vs 28°C, UCP1 and lipase gene expression, BAT weight, energy expenditure measurement, immunohistochemistry PloS one Medium 24066098
2015 BMP7 promotes self-renewal of nephron progenitor cells (NPCs) by activating MAPKs TAK1 and JNK to phosphorylate JUN, which governs AP-1-element containing G1-phase cell cycle regulators (Myc, Ccnd1); concurrent BMP7 (regulating JUN) and FGF9 (regulating FOS) signals coordinate AP-1 transcription to promote G1-S progression and NPC proliferation; conditional inactivation of Tak1 or Jun in cap mesenchyme causes premature NPC depletion. Conditional knockout of Tak1 and Jun in cap mesenchyme, BMP7 treatment of NPCs, phospho-JUN and phospho-TAK1 assays, cell cycle analysis Nature communications High 26634297
2015 Gremlin1 (Grem1) preferentially binds BMP-2 > BMP-4 > BMP-7; Grem1 affinity for BMP-7 is lower than for BMP-2 and BMP-4; Grem1 inhibits BMP-2/4 signaling by binding in solution preventing receptor activation, but cell-associated Grem1 does not inhibit BMP-2/4 signaling. Surface plasmon resonance, Smad1/5/8 phosphorylation assay in kidney proximal tubule and HEK-293 cells, cell culture BMP signaling readouts The Biochemical journal High 25378054
2015 The BMP7 and Tfap2c genes, though adjacent, are regulated by distinct non-overlapping sets of enhancers within separate topological domains demarcated by a discrete transition zone; engineered chromosomal rearrangements that disrupt this transition zone alter enhancer-gene allocation and gene expression. Engineered chromosomal rearrangements in mice, chromosome conformation capture (4C), in vivo reporter assays PLoS genetics High 25569170
2017 BMP-7 inhibits PI3K/Akt signaling during renal fibrosis by inducing PTEN expression; in the UUO model, BMP-7 maintains SMAD1/5/8 phosphorylation, attenuates SMAD3 and Akt signaling, and specifically inhibits TGFβ1/hypoxia-driven Akt activation in collecting duct and tubular epithelial cells via PTEN induction. UUO mouse model, rhBMP-7 treatment, Western blot for phospho-SMAD1/5/8, SMAD3, ERK, p38, Akt, PTEN; in vitro TGFβ1 and hypoxia stimulation of mIMCD and HK-2 cells Biochimica et biophysica acta. Molecular basis of disease High 28923783
2017 BMP7 induces uterine receptivity by suppressing estrogen-dependent signaling; conditional uterine knockout of BMP7 (Pgr-Cre) leads to subfertility with nonreceptive endometrium at implantation, defective decidualization (reduced Wnt4, Cox2, Ereg, Bmp2), and placental abnormalities. Conditional KO mice (Bmp7flox/flox-Pgr-Cre), fertility analysis, gene expression analysis, histology Endocrinology High 28324064
2018 In the lamina propria, BMP7 signals through ALK3 to promote translocation of LC precursors to the epithelium; within the epithelium, TGF-β1 via ALK5 finalizes LC differentiation; this two-step sequential signaling process is required for mucosal Langerhans cell differentiation. In vivo murine mucosal LC differentiation studies, ALK3/ALK5 receptor blocking, genetic models The Journal of experimental medicine High 29343501
2018 BMP7 inhibits TGFβ2-induced EMT in retinal pigment epithelial cells by balancing TGFβ2/Smad2/3 and BMP7/Smad1/5/9 pathways, maintaining RPE phenotype and reducing fibronectin, alpha-smooth muscle actin, and EMT-related migration; in vivo BMP7 injection attenuates PVR progression in rabbit. In vitro RPE cell TGFβ2 stimulation + BMP7 treatment, Western blot for Smad2/3 and Smad1/5/9, migration assay, gel contraction assay; rabbit PVR in vivo model FASEB journal High 30383450
2019 BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis: a knock-in mutation preventing proteolytic activation of dimerized BMP7 precursor (eliminating BMP7 homodimer and BMP7-containing heterodimer function) causes embryonic lethality with broadly reduced BMP activity; compound heterozygotes with Bmp2 or Bmp4 null alleles die with body wall and heart defects; endogenous BMP4/7 heterodimers confirmed by co-immunoprecipitation. Knock-in mouse with processing-preventing mutation, compound heterozygotes with Bmp2/Bmp4 null alleles, co-immunoprecipitation of endogenous heterodimers eLife High 31566563
2021 BMP7 attenuates diabetic cardiomyopathy by reducing inflammasome formation (TLR4, NLRP3, Nek7, GBP5), pyroptosis (caspase-1, IL-1β, IL-18), and inflammatory cytokines; BMP7 improves cardiac remodeling and LV function in STZ-induced diabetic mice, acting via the TLR4-NLRP3 inflammasome complex modulated by Nek7/GBP5 signaling. STZ-induced diabetic mouse model, BMP7 treatment, echocardiography, Western blot, immunostaining for inflammasome and pyroptosis markers Cells Medium 34685620
2024 BMP7 promotes cardiomyocyte proliferation and regeneration through BMPR1A/ACVR1 and ACVR2A/BMPR2 receptors and downstream SMAD5, ERK, and AKT signaling; Bmp7 knockdown in neonatal mouse cardiomyocytes and loss-of-function in adult zebrafish reduces cardiomyocyte proliferation, while BMP7 overexpression or administration post-myocardial infarction enhances cardiomyocyte cycling in vivo. Neonatal mouse cardiomyocyte Bmp7 knockdown, adult zebrafish cardiac regeneration loss-of-function, in vivo BMP7 administration post-MI, receptor identity established, Western blot for SMAD5/ERK/AKT Cell reports High 38678558
2014 BMP4 and BMP7 downregulate pentraxin 3 (PTX3) expression in human granulosa cells via Smad1/5/8 phosphorylation and Smad4-dependent signaling; BMP7 acts through ALK2/ALK3 receptors to mediate this effect, distinct from BMP4's use of ALK3/ALK6. siRNA knockdown of ALK2, ALK3, ALK6, Smad4; BMP receptor inhibitors (dorsomorphin, DMH-1); Western blot, RT-PCR, ELISA in SVOG, KGN, and primary granulosa-lutein cells The Journal of clinical endocrinology and metabolism High 25514099
2011 Mechanical loading (pulsating fluid flow) upregulates BMP7 (but not BMP2) gene and protein expression in human osteocytes in vitro; this mechanically induced BMP7 upregulation requires the vitamin D receptor (VDR), as it is absent in VDR-/- mouse bone cells. Pulsating fluid flow on human and VDR-/- mouse primary bone cells, RT-PCR, ELISA for BMP2 and BMP7 Calcified tissue international Medium 21842277

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 OP-1 cDNA encodes an osteogenic protein in the TGF-beta family. The EMBO journal 510 2357959
2006 Genetic analysis of the roles of BMP2, BMP4, and BMP7 in limb patterning and skeletogenesis. PLoS genetics 481 17194222
1999 Osteogenic activity of OP-1 bone morphogenetic protein (BMP-7) in a human fibular defect. The Journal of bone and joint surgery. British volume 237 10463751
2000 Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development (Cambridge, England) 228 10662635
2007 Clinical applications of BMP-7/OP-1 in fractures, nonunions and spinal fusion. International orthopaedics 208 17962946
2006 Osteogenesis versus chondrogenesis by BMP-2 and BMP-7 in adipose stem cells. Biochemical and biophysical research communications 193 16500625
1997 BMP7 null mutation in mice: developmental defects in skeleton, kidney, and eye. Experimental cell research 190 9013703
2000 Essential role of Bmp7 (snailhouse) and its prodomain in dorsoventral patterning of the zebrafish embryo. Development (Cambridge, England) 180 10603351
2001 Bmp6 and Bmp7 are required for cushion formation and septation in the developing mouse heart. Developmental biology 170 11437450
1991 Murine osteogenic protein (OP-1): high levels of mRNA in kidney. Biochemical and biophysical research communications 164 1715687
2007 OP-1/BMP-7 in cartilage repair. International orthopaedics 146 17687553
2003 Loss of Bmp7 and Fgf8 signaling in Hoxa13-mutant mice causes hypospadia. Development (Cambridge, England) 145 12783783
2013 BMP4 and BMP7 induce the white-to-brown transition of primary human adipose stem cells. American journal of physiology. Cell physiology 141 24284793
2012 Delivery of PDGF-B and BMP-7 by mesoporous bioglass/silk fibrin scaffolds for the repair of osteoporotic defects. Biomaterials 135 22763224
2006 Adenovirus-mediated expression of BMP-7 suppresses the development of liver fibrosis in rats. Gut 134 17127702
1998 Regulation of BMP7 expression during kidney development. Development (Cambridge, England) 127 9693150
2013 SMAD-PI3K-Akt-mTOR pathway mediates BMP-7 polarization of monocytes into M2 macrophages. PloS one 118 24376781
1999 Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 113 10418861
2008 BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer letters 102 18980801
2001 Traumatic injury-induced BMP7 expression in the adult rat spinal cord. Brain research 96 11720729
2006 A comprehensive expression survey of bone morphogenetic proteins in breast cancer highlights the importance of BMP4 and BMP7. Breast cancer research and treatment 93 17004110
2007 TGF-beta and BMP7 interactions in tumour progression and bone metastasis. Clinical & experimental metastasis 89 18008174
2006 Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. International orthopaedics 89 16506027
2007 Endoglin differentially modulates antagonistic transforming growth factor-beta1 and BMP-7 signaling. The Journal of biological chemistry 86 17376778
2008 Epigenetic regulation of BMP7 in the regenerative response to ischemia. Journal of the American Society of Nephrology : JASN 85 18322163
1997 Regulation of epidermal induction by BMP2 and BMP7 signaling. Developmental biology 85 9281341
2013 Identification of bone morphogenetic protein 7 (BMP7) as an instructive factor for human epidermal Langerhans cell differentiation. The Journal of experimental medicine 83 24190429
2015 Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4 over BMP-7. The Biochemical journal 82 25378054
2003 A pilot safety and efficacy study of OP-1 putty (rhBMP-7) as an adjunct to iliac crest autograft in posterolateral lumbar fusions. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 81 12908103
2013 Fine-tuning BMP7 signalling in adipogenesis by UBE2O/E2-230K-mediated monoubiquitination of SMAD6. The EMBO journal 80 23455153
2007 BMP7 is a podocyte survival factor and rescues podocytes from diabetic injury. American journal of physiology. Renal physiology 79 17804487
2009 BMP-7 as antagonist of organ fibrosis. Frontiers in bioscience (Landmark edition) 77 19482601
2008 Reversal of experimental renal fibrosis by BMP7 provides insights into novel therapeutic strategies for chronic kidney disease. Pediatric nephrology (Berlin, Germany) 76 18446379
1999 The safety of OP-1 for lumbar fusion with decompression-- a canine study. Neurosurgery 76 10232555
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2008 Clinical significance of BMP7 in human colorectal cancer. Annals of surgical oncology 72 18259822
2005 Neuroregenerative effects of BMP7 after stroke in rats. Journal of the neurological sciences 70 16236321
2001 Mutation in Bmp7 exacerbates the phenotype of Bmp8a mutants in spermatogenesis and epididymis. Developmental biology 68 11784057
2020 The Role of Bone Morphogenetic Protein 7 (BMP-7) in Inflammation in Heart Diseases. Cells 67 31979268
2008 BMP2 and BMP7 play antagonistic roles in feather induction. Development (Cambridge, England) 66 18635609
2017 BMP7-induced-Pten inhibits Akt and prevents renal fibrosis. Biochimica et biophysica acta. Molecular basis of disease 62 28923783
2005 BMP7 signaling in renal development and disease. Trends in molecular medicine 62 16216558
2009 BDNF/MAPK/ERK-induced BMP7 expression in the developing cerebral cortex induces premature radial glia differentiation and impairs neuronal migration. Cerebral cortex (New York, N.Y. : 1991) 61 20038543
2011 Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis. Growth factors (Chur, Switzerland) 60 21591998
2021 BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy. Cells 59 34685620
2007 FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. European journal of human genetics : EJHG 59 17264867
2017 BMP7 Induces Uterine Receptivity and Blastocyst Attachment. Endocrinology 52 28324064
2008 Podocyte-derived BMP7 is critical for nephron development. Journal of the American Society of Nephrology : JASN 52 18923055
2018 Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation. The Journal of experimental medicine 50 29343501
1992 A bone morphogenetic protein subfamily: chromosomal localization of human genes for BMP5, BMP6, and BMP7. Genomics 50 1427904
2015 A discrete transition zone organizes the topological and regulatory autonomy of the adjacent tfap2c and bmp7 genes. PLoS genetics 49 25569170
2008 Bone morphogenetic protein-7 (BMP7) in chronic kidney disease. Frontiers in bioscience : a journal and virtual library 48 18508541
2015 Lysine-specific demethylase 5C promotes hepatocellular carcinoma cell invasion through inhibition BMP7 expression. BMC cancer 46 26503415
2015 Concurrent BMP7 and FGF9 signalling governs AP-1 function to promote self-renewal of nephron progenitor cells. Nature communications 46 26634297
2007 Anti-catabolic effect of OP-1 in chronically compressed intervertebral discs. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 46 17205567
2006 Mutation screening of BMP4, BMP7, HOXA4 and HOXB6 genes in Chinese patients with hypospadias. European journal of human genetics : EJHG 46 17003840
2004 BMP-7 modulates hyaluronan-mediated proximal tubular cell-monocyte interaction. Journal of the American Society of Nephrology : JASN 46 15100360
2016 ITF2357 transactivates Id3 and regulate TGFβ/BMP7 signaling pathways to attenuate corneal fibrosis. Scientific reports 45 26865052
2002 Regulation of BMP-7 expression by retinoic acid and prostaglandin E(2). Journal of cellular physiology 45 11807825
2009 Trps1 functions downstream of Bmp7 in kidney development. Journal of the American Society of Nephrology : JASN 44 19820125
2007 Effects of OP-1 and PTH in a new experimental model for the study of metaphyseal bone healing. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 44 17506507
2007 The protective effect of OP-1 on articular cartilage in the development of osteoarthritis. Osteoarthritis and cartilage 44 17977753
2002 Differential effect of activin A and BMP-7 on myofibroblast differentiation and the role of the Smad signaling pathway. Investigative ophthalmology & visual science 43 11773015
2019 BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis. eLife 42 31566563
2009 Levels of expression for BMP-7 and several BMP antagonists may play an integral role in a fracture nonunion: a pilot study. Clinical orthopaedics and related research 40 19597895
2021 Ultrasound triggered topical delivery of Bmp7 mRNA for white fat browning induction via engineered smart exosomes. Journal of nanobiotechnology 39 34863187
2018 BMP7 antagonizes proliferative vitreoretinopathy through retinal pigment epithelial fibrosis in vivo and in vitro. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 38 30383450
2014 Recombinant BMP4 and BMP7 downregulate pentraxin 3 in human granulosa cells. The Journal of clinical endocrinology and metabolism 38 25514099
2015 MiR-22 Suppresses BMP7 in the Development of Cirrhosis. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 37 26112332
2004 Expression of bone morphogenetic protein-7 (BMP-7) in human prostate. The Prostate 37 14991870
2011 BMP-2 and BMP-7 affect human rotator cuff tendon cells in vitro. Journal of shoulder and elbow surgery 36 21454098
2009 ActRIIA and BMPRII Type II BMP receptor subunits selectively required for Smad4-independent BMP7-evoked chemotaxis. PloS one 36 20011660
2013 The etiology of cleft palate formation in BMP7-deficient mice. PloS one 35 23516636
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2019 Differentiating SGBS adipocytes respond to PPARγ stimulation, irisin and BMP7 by functional browning and beige characteristics. Scientific reports 32 30967578
2017 MicroRNA-137 inhibits BMP7 to enhance the epithelial-mesenchymal transition of breast cancer cells. Oncotarget 32 28407692
2011 Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes. Calcified tissue international 32 21842277
2008 Cell therapy using articular chondrocytes overexpressing BMP-7 or BMP-10 in a rabbit disc organ culture model. Spine 31 18404100
2021 RIP1 Perturbation Induces Chondrocyte Necroptosis and Promotes Osteoarthritis Pathogenesis via Targeting BMP7. Frontiers in cell and developmental biology 30 33937236
2019 Targeting chemoresistant colorectal cancer via systemic administration of a BMP7 variant. Oncogene 30 31591478
2015 Mesenchymal stem cells mitigate cirrhosis through BMP7. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 30 25613158
2018 MiR-542-3p controls hepatic stellate cell activation and fibrosis via targeting BMP-7. Journal of cellular biochemistry 28 30368874
2019 Genomic Analysis Reveals Pleiotropic Alleles at EDN3 and BMP7 Involved in Chicken Comb Color and Egg Production. Frontiers in genetics 27 31316551
2014 Exogenous BMP7 corrects plasma iron overload and bone loss in Bmp6-/- mice. International orthopaedics 27 25300398
2011 Clinicopathological significance of BMP7 expression in esophageal squamous cell carcinoma. Annals of surgical oncology 27 21913019
2009 Generation and functional characterization of mice with a conditional BMP7 allele. The International journal of developmental biology 27 19247966
2003 The interaction of BMP-7 and ActRII implicates a new mode of receptor assembly. Trends in biochemical sciences 25 14559178
2003 No augmentation of morselized and impacted bone graft by OP-1 in a weight-bearing model. Acta orthopaedica Scandinavica 25 14763709
2019 Effects of Sprifermin, IGF1, IGF2, BMP7, or CNP on Bovine Chondrocytes in Monolayer and 3D Culture. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 24 31608492
2018 Mm9_circ_009056 enhances osteogenesis by targeting BMP7 via CGRP-mediated miR-22-3p. Biochemical and biophysical research communications 24 29709471
2017 Microglia activation is essential for BMP7-mediated retinal reactive gliosis. Journal of neuroinflammation 24 28381236
2012 BMP signaling in rats with TNBS-induced colitis following BMP7 therapy. American journal of physiology. Gastrointestinal and liver physiology 24 22361727
2010 Enhanced healing of goat femur-defect using BMP7 gene-modified BMSCs and load-bearing tissue-engineered bone. Journal of orthopaedic research : official publication of the Orthopaedic Research Society 24 19725097
2020 Differences in Transforming Growth Factor-β1/BMP7 Signaling and Venous Fibrosis Contribute to Female Sex Differences in Arteriovenous Fistulas. Journal of the American Heart Association 23 32757791
2014 Molecular characterization of the BMP7 gene and its potential role in shell formation in Pinctada martensii. International journal of molecular sciences 23 25407527
2009 Biocompatibility and safety of a hybrid core-shell nanoparticulate OP-1 delivery system intramuscularly administered in rats. Biomaterials 23 20044132
2009 Neuroprotective effects of bone morphogenetic protein 7 (BMP7) treatment after spinal cord injury. Neuroscience letters 22 19765637
2024 BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice. Cell reports 21 38678558
2022 AAV-mediated BMP7 gene therapy counteracts insulin resistance and obesity. Molecular therapy. Methods & clinical development 21 35434177