Affinage

BMP7

Bone morphogenetic protein 7 · UniProt P18075

Length
431 aa
Mass
49.3 kDa
Annotated
2026-06-09
100 papers in source corpus 32 papers cited in narrative 32 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

BMP7 (OP-1) is a secreted TGF-beta superfamily ligand, originally identified as an osteogenic protein with sequence homology to DPP and Vg-1 (PMID:2357959), that orchestrates organ development, tissue homeostasis, and fibrosis suppression. In vivo it functions predominantly as a heterodimer with BMP2/BMP4: blocking BMP7 proteolytic activation causes embryonic lethality with broadly reduced BMP activity, and endogenous BMP4/BMP7 heterodimers are detectable in vivo (PMID:31566563), a synergy genetically established in zebrafish dorsoventral patterning (PMID:10662635). BMP7 assembles a cooperative receptor complex with activin/BMP type II receptors and signals through type I receptors—predominantly ALK3/BMPR1A and ACVR1—to phosphorylate SMAD1/5/8 (PMID:14559178, PMID:26302112, PMID:24190429, PMID:38678558). Beyond canonical SMAD signaling, BMP7 directly activates non-canonical cascades: TAK1/JNK to phosphorylate JUN/ATF2 and drive AP-1-dependent G1 cell cycle genes (Myc, Ccnd1) for nephron progenitor proliferation (PMID:19793891, PMID:26634297), and SMAD5/ERK/AKT to stimulate cardiomyocyte proliferation including after myocardial infarction (PMID:38678558). BMP7 directs diverse developmental programs—lens placode induction upstream of Pax6 (PMID:10049573), cardiac cushion formation redundantly with BMP6 (PMID:11437450), spermatogenesis redundantly with BMP8a (PMID:11784057), cloacal septation via JNK-dependent division polarity (PMID:22253716), Langerhans cell differentiation through ALK3 (PMID:24190429, PMID:29343501), and uterine receptivity and implantation (PMID:28324064). A central theme is antagonism of TGF-beta/SMAD2/3-driven fibrosis, achieved by maintaining MMP2 and suppressing PAI-1 (PMID:12676736), upregulating PTEN while inhibiting AKT (PMID:28923783), and downregulating miR-21 to elevate SMAD7 (PMID:31655195). BMP7 signaling is modulated by extracellular binding partners CTGF (PMID:18632843), Gremlin1 (PMID:25378054), SPARCL1 (PMID:31699966), and endoglin (PMID:17376778). Centrally administered BMP7 also suppresses appetite via a rapamycin-sensitive mTOR-p70S6K pathway (PMID:22331196).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1990 High

    Established BMP7's molecular identity as a secreted TGF-beta superfamily osteogenic protein, defining the entity all subsequent work would characterize.

    Evidence cDNA cloning and tryptic peptide sequencing from bovine osteogenic protein preparations with genomic library screening

    PMID:2357959

    Open questions at the time
    • Did not establish receptors or downstream signaling
    • No in vivo functional role defined
  2. 1997 Medium

    Showed BMP7 acts directly on kidney epithelium through a distinct ~80 kDa receptor to control branching morphogenesis in a dose-dependent manner, linking the ligand to organogenesis.

    Evidence Ligand-receptor affinity assays and embryonic kidney explant branching cultures in mIMCD-3 cells

    PMID:9435686

    Open questions at the time
    • Receptor identity not molecularly defined
    • Intracellular signaling not delineated
  3. 1999 High

    Defined a developmental epistasis placing BMP7 upstream of Pax6 in lens placode induction, addressing how BMP7 specifies eye fate.

    Evidence Mouse knockout, in vitro antagonist experiments, in situ hybridization and immunolocalization

    PMID:10049573

    Open questions at the time
    • Receptor and SMAD effectors in lens ectoderm not identified
  4. 2000 High

    Demonstrated BMP7/BMP2b functional synergy in dorsoventral patterning, providing early in vivo evidence for heterodimeric BMP action.

    Evidence Zebrafish null mutants, double-mutant epistasis, rescue and overexpression synergy

    PMID:10662635

    Open questions at the time
    • Biochemical confirmation of heterodimer not provided in this system
  5. 2001 High

    Revealed genetic redundancy of BMP7 with BMP6 (cardiac cushions) and BMP8a (spermatogenesis), explaining why single mutants spare certain organs and implying shared receptors.

    Evidence Mouse double-knockout genetics and embryonic phenotype analysis

    PMID:11437450 PMID:11784057

    Open questions at the time
    • Molecular basis of redundancy and shared receptor identity not resolved
  6. 2003 Medium

    Provided a structural paradigm for how BMP7 assembles type II receptors cooperatively without receptor-receptor contacts, and a cellular mechanism for anti-fibrotic action via MMP2/PAI-1.

    Evidence Crystal structure of BMP7-ActRII complex; mesangial cell reporter and MMP activity assays

    PMID:12676736 PMID:14559178

    Open questions at the time
    • Structure is of a partial complex (type II receptor only)
    • Anti-fibrotic mechanism inferred from protein-level changes without mRNA changes
  7. 2007 Medium

    Established the antagonistic logic between BMP7 (SMAD1/5) and TGF-beta1 (ALK5/SMAD3), and identified endoglin as a modulator favoring BMP7 signaling.

    Evidence Transient transfection, luciferase reporters, SMAD phosphorylation Western blots; podocyte loss/gain-of-function for SMAD5 survival role

    PMID:17376778 PMID:17804487

    Open questions at the time
    • Single-lab reporter-based studies
    • Receptor-level basis of SMAD5 versus SMAD1 selectivity unresolved
  8. 2008 High

    Identified CTGF as a high-affinity BMP7 binding antagonist that blunts pSmad1/5 signaling in diabetic kidney, defining an extracellular brake on BMP7.

    Evidence Co-IP, solid-phase binding, surface plasmon resonance, and in vivo mouse models

    PMID:18632843

    Open questions at the time
    • Binding interface not mapped
    • Therapeutic reversibility in vivo not fully defined
  9. 2009 High

    Showed BMP7 directly activates non-canonical TAK1/JNK signaling to phosphorylate JUN/ATF2 and drive nephron progenitor proliferation, expanding BMP7 effectors beyond SMADs.

    Evidence Primary progenitor isolation, phosphorylation assays, Bmp7-null kidney validation; hyaluronan/CD44 monocyte-binding assays in tubular cells

    PMID:15100360 PMID:19793891

    Open questions at the time
    • Direct receptor coupling to TAK1 not biochemically traced
    • Relationship of JNK arm to SMAD arm unresolved
  10. 2013 High

    Defined ALK3 as the type I receptor for BMP7-driven Langerhans cell differentiation and dissected its relationship to TGF-beta1/ALK5, while extending non-canonical signaling to PI3K-Akt-mTOR macrophage polarization and corneal anti-fibrosis.

    Evidence Bmp7-knockout mice, ALK3/ALK5 inhibitors, PI3K inhibition, in vivo corneal gene delivery

    PMID:23799103 PMID:24190429 PMID:24376781

    Open questions at the time
    • Cross-talk between SMAD, PI3K, and JNK arms not integrated
    • Cell-type specificity of receptor usage not fully explained
  11. 2015 High

    Refined the nephron progenitor mechanism (BMP7/TAK1/JUN coordinating with FGF9/FOS for AP-1) and established ALK3/SMAD4 dependence and Gremlin1 binding selectivity for BMP7 in defined cell systems.

    Evidence Conditional Tak1/Jun knockouts with epistasis; siRNA receptor depletion and inhibitors in granulosa-lutein cells; surface plasmon resonance for Grem1

    PMID:25378054 PMID:26302112 PMID:26634297

    Open questions at the time
    • How AP-1 inputs are integrated transcriptionally not fully mapped
    • Physiological role of low-affinity Grem1-BMP7 binding uncertain
  12. 2017 Medium

    Mechanistically connected BMP7's anti-fibrotic action to PTEN upregulation and Akt/SMAD3 inhibition, and defined a role in uterine receptivity and implantation.

    Evidence UUO mouse model with phospho-signaling analysis; conditional Bmp7 knockout in female reproductive tract

    PMID:28324064 PMID:28923783

    Open questions at the time
    • Direct link between BMP7 receptors and PTEN induction not established
    • Implantation effectors downstream of BMP7 only partially defined
  13. 2019 High

    Consolidated heterodimer biology in mammalian embryogenesis and added miR-21/SMAD7 and SPARCL1/YY1 regulatory axes, integrating BMP7 into cardiac and renal fibrosis control.

    Evidence Knock-in proteolytic-mutant mice and Co-IP for endogenous heterodimers; miR-21 gain/loss-of-function; SPARCL1 Co-IP and CRISPR knockout; in vivo DCM model with BMP7 knockdown

    PMID:31495264 PMID:31566563 PMID:31655195 PMID:31699966

    Open questions at the time
    • Relative contribution of homodimer versus heterodimer per tissue unresolved
    • Direct versus indirect effects of YY1/SPARCL1 on BMP7 not separated
  14. 2024 High

    Established BMP7 as a cardiomyocyte proliferation factor acting through BMPR1A/ACVR1 and ACVR2A/BMPR2 with SMAD5/ERK/AKT output, with regenerative potential after myocardial infarction.

    Evidence Neonatal mouse knockdown, adult zebrafish loss-of-function, overexpression, in vivo MI model with receptor and signaling identification

    PMID:38678558

    Open questions at the time
    • Durability and safety of regenerative effect not established
    • Heterodimer requirement in cardiomyocytes not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How BMP7 selects among canonical (SMAD1/5/8) and non-canonical (JNK/TAK1, ERK, AKT, mTOR) outputs in a given cell type, and how homodimer versus BMP2/4-heterodimer states are partitioned across tissues, remains unresolved.
  • No unified model linking receptor composition to effector choice
  • Quantitative tissue-by-tissue homodimer/heterodimer mapping absent
  • Full-complex (type I + type II) structure with heterodimeric ligand not resolved in timeline

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0048018 receptor ligand activity 5 GO:0060089 molecular transducer activity 5 GO:0098772 molecular function regulator activity 5
Localization
GO:0005576 extracellular region 4 GO:0031012 extracellular matrix 1
Pathway
R-HSA-1266738 Developmental Biology 5 R-HSA-162582 Signal Transduction 5 R-HSA-1643685 Disease 4
Partners
ACVR2ABMP2BMP4BMPR1ACTGFENGGREM1SPARCL1

Evidence

Reading pass · 32 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 BMP7 (OP-1) was identified as a member of the TGF-beta superfamily based on amino acid sequence homology of tryptic peptides from bovine osteogenic protein preparations to DPP (Drosophila) and Vg-1 (Xenopus), and its cDNA was cloned from human genomic libraries, establishing its primary structure as a secreted osteogenic protein. cDNA cloning, amino acid sequencing, genomic library screening The EMBO journal High 2357959
2019 BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis. A knock-in mutation preventing proteolytic activation of BMP7 (eliminating homodimer and heterodimer function) caused embryonic lethality with broadly reduced BMP activity, and co-immunoprecipitation confirmed endogenous BMP4/BMP7 heterodimers exist in vivo. Knock-in mouse genetics, co-immunoprecipitation, compound heterozygote analysis eLife High 31566563
2003 The crystal structure of BMP7 in complex with the extracellular domain of activin type II receptor (ActRII) revealed a novel mode of ligand-mediated cooperative receptor assembly without receptor-receptor contacts, providing mechanistic insight into TGF-beta superfamily signal transduction. Structural analysis (crystal structure of BMP7-ActRII complex) Trends in biochemical sciences Medium 14559178
2009 BMP7 directly and rapidly activates JNK signaling in nephron progenitor cells, resulting in phosphorylation of Jun and ATF2 transcription factors, accumulation of cyclin D3, and subsequent proliferation of PAX2+ progenitors. This was demonstrated using primary progenitor isolation and confirmed in vivo in Bmp7-null kidneys where Jun and ATF2 phosphorylation was severely diminished. Primary cell isolation, signaling assays (phosphorylation), Bmp7-null mouse analysis Development (Cambridge, England) High 19793891
2015 BMP7 activates the MAPKs TAK1 and JNK to phosphorylate the transcription factor JUN, which governs transcription of AP-1-element containing G1-phase cell cycle regulators (Myc, Ccnd1) to promote nephron progenitor cell (NPC) proliferation. BMP7 regulates JUN while FGF9 regulates FOS, and these two signals coordinately regulate AP-1 transcription. Conditional inactivation of Tak1 or Jun in cap mesenchyme caused identical phenotypes with premature NPC depletion. Conditional knockout mouse genetics, epistasis analysis, transcription factor phosphorylation assays Nature communications High 26634297
2003 BMP7 antagonizes TGF-beta-induced fibrogenesis in mesangial cells primarily by maintaining MMP2 levels and activity, partly through prevention of TGF-beta-dependent upregulation of PAI-1. BMP7 reduced TGF-beta-induced ECM protein (collagen IV, fibronectin) accumulation without concomitant changes in mRNA, suggesting action at the level of ECM protein degradation. Cell culture, luciferase reporter assay (PAI-1 promoter), MMP activity assays, protein quantification American journal of physiology. Renal physiology Medium 12676736
2008 CTGF binds BMP7 with high affinity (Kd ~14 nM) as shown by co-immunoprecipitation, solid-phase binding assay, and surface plasmon resonance, and thereby inhibits BMP7 signal transduction (reduced pSmad1/5, Id1 expression) in the diabetic kidney, contributing to diabetic nephropathy. Co-immunoprecipitation, solid-phase binding assay, surface plasmon resonance, in vivo mouse models Journal of the American Society of Nephrology : JASN High 18632843
2007 Endoglin enhances BMP7/Smad1/Smad5 signaling while inhibiting TGF-beta1-induced ALK-5/Smad3 signaling. BMP7 exclusively activates Smad1/Smad5 (not Smad3) and antagonizes TGF-beta1-induced collagen I expression mediated by the ALK-5/Smad3 pathway, establishing the opposing signaling mechanisms of BMP7 and TGF-beta1. Transient transfection, luciferase reporter assay, Western blot for Smad phosphorylation The Journal of biological chemistry Medium 17376778
2013 BMP7 polarizes monocytes into M2 macrophages via a SMAD-PI3K-Akt-mTOR pathway. BMP7 treatment increased p-SMAD1/5/8 and p-PI3K, leading to downstream Akt and mTOR activation, and inhibited PTEN expression. PI3K inhibition (LY-294002) reduced BMP7-induced M2 polarization markers. Cell culture, Western blot (phospho-signaling), PI3K inhibitor, immunostaining PloS one Medium 24376781
2007 BMP7 (OP-1) is a podocyte survival factor acting via Smad5 (not Smad1). High glucose reduces BMP7 secretion/activity in podocytes; BMP7 activates Smad5 and p38, and blocks high glucose/TGF-beta-induced caspase-3 activation and apoptosis. Knockdown and forced expression studies confirmed Smad5 is necessary and sufficient for BMP7's survival effects. Cell culture, RNA interference (knockdown), forced expression, apoptosis assays, Smad phosphorylation American journal of physiology. Renal physiology Medium 17804487
2013 BMP7 inhibits corneal fibrosis by counterbalancing TGFβ1-mediated profibrotic Smad signaling; BMP7-transfected human corneal fibroblasts showed significantly increased pSmad-1/5/8 nuclear localization and Smad6 expression, with decreased α-SMA, reducing myofibroblast formation in vivo. In vivo gene delivery (rabbit), immunofluorescence, Western blot, nanoparticle transfection PloS one Medium 23799103
2012 BMP7 reverses obesity and regulates appetite through a central mTOR pathway. Intracerebroventricular BMP7 acutely decreased food intake via a rapamycin-sensitive mTOR-p70S6K pathway, independent of leptin, as shown in diet-induced obese and ob/ob mice. Intracerebroventricular injection, mTOR pathway inhibition (rapamycin), diet-induced obese and ob/ob mouse models FASEB journal Medium 22331196
2017 BMP7 inhibits PI3K/Akt signaling and upregulates PTEN to prevent renal fibrosis. In the UUO model, BMP7 activated SMAD1/5/8 in renal collecting duct/tubular epithelial cells and specifically attenuated SMAD3 and Akt signaling in vivo. BMP7 increased PTEN expression in vivo and in vitro, identifying a mechanism by which BMP7 inhibits fibrogenesis through Akt inhibition. In vivo mouse model (UUO), primary cell culture, Western blot (phospho-signaling), gene expression Biochimica et biophysica acta. Molecular basis of disease Medium 28923783
2000 In zebrafish, bmp7/snailhouse and bmp2b/swirl have equivalent genetic roles in dorsoventral patterning, and overexpression experiments show Bmp2b and Bmp7 synergize in ventralization through a cell-autonomous mechanism, suggesting BMP2b/BMP7 heterodimers act in vivo to specify ventral cell fates. Zebrafish genetics (null mutants, overexpression), epistasis (double mutants), rescue experiments Development (Cambridge, England) High 10662635
2001 Bmp7 plays a role in spermatogenesis and epididymal function genetically redundant with Bmp8a; removal of one Bmp7 allele exacerbates the Bmp8a null phenotype, indicating BMP8 and BMP7 signal through the same or similar receptors in these systems. Mouse genetics (double mutant epistasis analysis) Developmental biology Medium 11784057
1999 BMP7 is required for lens placode development upstream of Pax6; BMP7 protein is present in head ectoderm at the time of lens placode induction, and addition of BMP7 antagonists in vitro inhibits lens formation. In Bmp7 mutant embryos, Pax6 head ectoderm expression is lost just prior to lens placode formation, while Bmp7 expression is maintained in Sey/Sey (Pax6-deficient) embryos. Mouse knockout, in vitro antagonist experiments, in situ hybridization, immunolocalization Developmental biology High 10049573
2001 Bmp6 and Bmp7 function redundantly in cardiac cushion formation; neither single mutant has cardiac defects, but Bmp6;Bmp7 double mutants show marked delay in outflow tract endocardial cushion formation, defects in valve morphogenesis/septation, and embryonic lethality. Mouse double knockout genetics, embryonic phenotype analysis Developmental biology High 11437450
1997 OP-1 (BMP7) bound to an ~80 kDa receptor protein in mIMCD-3 kidney epithelial cells (distinct from ALK-3 which binds BMP-2), and at low doses promoted renal branching morphogenesis (increasing tubular structures and branch points), while high doses were inhibitory—demonstrating dose-dependent, direct effects on kidney branching. Ligand-receptor affinity assays, embryonic kidney explant culture, in vitro branching morphogenesis model The American journal of physiology Medium 9435686
1997 BMP7 and BMP2 regulate epidermal induction in Xenopus embryos through a common receptor (XALK2/BMP2/7 receptor). A constitutively active XALK2 mutant inhibited neuralization and induced epidermis in a ligand-independent manner, and dominant-negative BMP2 ligand caused neuralization, demonstrating BMP7 participates in inhibition of neural fate. Xenopus embryo injection, constitutively active/dominant-negative receptor constructs, ectodermal dissociation assays Developmental biology Medium 9281341
2013 BMP7 induces Langerhans cell (LC) differentiation and proliferation by activating BMP type-I receptor ALK3 in the absence of canonical TGF-β1-ALK5 signaling. Bmp7-deficient mice exhibit substantially diminished LC numbers. BMP7 and TGF-β1 both signal through ALK3 for LC generation, but co-induction of ALK5 by TGF-β1 diminishes LC yields. Bmp7 knockout mouse analysis, in vitro LC differentiation with ALK3/ALK5 inhibitors The Journal of experimental medicine High 24190429
2018 Sequential BMP7-ALK3 signaling promotes LC precursor translocation to the epithelium (lamina propria stage), followed by TGF-β1-ALK5 signaling that finalizes LC differentiation within the epithelium—establishing a two-step mechanism for mucosal LC development. Mouse conditional genetics, intravital imaging, receptor-specific inhibition The Journal of experimental medicine Medium 29343501
2015 Gremlin1 (Grem1) binds BMP7 with lower affinity than BMP-2 or BMP-4 (BMP-2 > BMP-4 > BMP-7), as measured by surface plasmon resonance and cell culture Smad1/5/8 phosphorylation assays. Cell-associated Grem1 did not inhibit BMP-2 or BMP-4 signaling, suggesting Grem1-BMP binding occurs in solution. Surface plasmon resonance, cell-based Smad phosphorylation assays, BMP-responsive gene expression The Biochemical journal High 25378054
2015 BMP7 suppresses progesterone and StAR expression in human granulosa-lutein cells via ALK3 and SMAD1/5/8-SMAD4 signaling. siRNA depletion of ALK3 (but not ALK2 or ALK6) reversed BMP7-induced Smad1/5/8 phosphorylation and StAR suppression; Smad4 knockdown abolished BMP7 effects. siRNA knockdown, ALK receptor inhibitors (dorsomorphin, DMH1), Western blot, steroid quantification Endocrinology High 26302112
2013 BMP7 and BMP4 both down-regulate Cx43 expression and decrease gap junction intercellular communication (GJIC) in human granulosa cells via a Smad-dependent pathway. Dorsomorphin (BMP type I receptor inhibitor) and Smad4 siRNA both reversed the suppressive effects on Cx43. siRNA knockdown, pharmacological inhibition, RT-qPCR, Western blot, dye transfer assay The Journal of clinical endocrinology and metabolism Medium 23386650
2019 BMP7 decreases renal fibrosis in diabetic nephropathy by downregulating miR-21, which in turn upregulates Smad7, reducing Smad3 phosphorylation and preventing EMT and ECM deposition. In vitro miR-21 overexpression reversed BMP7 protective effects without affecting BMP7 levels. Cell culture, in vivo diabetic mouse model, miRNA overexpression/inhibition, Western blot Life sciences Medium 31655195
2012 Bmp7 cloacal septation function is mediated through JNK pathway activation. Loss of Bmp7 causes decreased endoderm survival, delayed differentiation, and randomization of mitotic spindle angles in cloacal endoderm. BMP7/JNK signaling establishes apical-basal cell division polarity required for cloacal partitioning. This mechanism is conserved in human fetal tissue. Mouse null embryo analysis, TUNEL, immunofluorescence, confocal 3D imaging of mitotic angles, immunohistochemistry (human fetal) PloS one Medium 22253716
2019 SPARCL1 binds BMP7 (confirmed by co-immunoprecipitation) and regulates BMP/TGF-β cell signaling, promoting C2C12 cell differentiation. SPARCL1 influences BMP7 expression, and SPARCL1 activation with BMP7 inhibition confirmed that SPARCL1 promotes differentiation through the BMP7/BMP-TGF-β pathway. Co-immunoprecipitation, CRISPR/Cas9 knockout, Western blot, immunofluorescence Cell death & disease Medium 31699966
2024 BMP7 stimulates cardiomyocyte proliferation 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 reduced cardiomyocyte proliferation; BMP7 administration in vivo following myocardial infarction enhanced cardiomyocyte cycling. Knockdown (neonatal mouse), zebrafish loss-of-function, overexpression, in vivo MI model, receptor identification, signaling pathway analysis Cell reports High 38678558
2019 YY1 suppresses dilated cardiomyopathy and cardiac fibrosis by inducing Bmp7 expression and preventing Ctgf upregulation. Knockdown of BMP7 attenuated Yy1's suppressive effect on DCM; upregulation of Bmp7 alone was insufficient—combined Bmp7 upregulation and Ctgf silencing was required—and acted by suppressing TGF-β/Smad signaling. Mouse model of DCM (shRNA-mediated Lmna silencing), in vivo BMP7 knockdown, reporter assays, Western blot Circulation research Medium 31495264
2017 BMP7 induces uterine receptivity and blastocyst implantation. Conditional BMP7 knockout in the female reproductive tract (Bmp7flox/flox-Pgr-cre) resulted in a nonreceptive endometrium with elevated estrogen-dependent signaling, failed decidualization, and reduced expression of decidual markers (Wnt4, Cox2, Ereg, Bmp2), as well as placental abnormalities. Conditional knockout mouse (Cre-lox), endometrial implantation assays, gene expression profiling Endocrinology Medium 28324064
2011 Mechanical loading (pulsating fluid flow) upregulates BMP7 (but not BMP2) gene and protein expression in osteocytes via a mechanism requiring the vitamin D receptor (VDR), as BMP7 upregulation was absent in VDR-knockout mouse bone cells. Primary bone cell culture, pulsating fluid flow, VDR-knockout mouse cells, gene/protein expression Calcified tissue international Medium 21842277
2009 BMP7 modulates hyaluronan-mediated proximal tubular cell-monocyte interaction by inducing HAS2 mRNA expression, decreasing Hyal1 and Hyal2 expression, increasing cell-associated hyaluronan cable formation, and enhancing CD44-dependent monocyte binding—distinct from IL-1β which increased soluble HA and ICAM-dependent binding. Cell culture (HK-2), radiolabeled monocyte binding assay, mRNA expression analysis Journal of the American Society of Nephrology : JASN Medium 15100360

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
1997 Role of BMP-2 and OP-1 (BMP-7) in programmed cell death and skeletogenesis during chick limb development. Development (Cambridge, England) 293 9102298
2000 Equivalent genetic roles for bmp7/snailhouse and bmp2b/swirl in dorsoventral pattern formation. Development (Cambridge, England) 228 10662635
1999 BMP7 acts in murine lens placode development. Developmental biology 219 10049573
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 194 16500625
1997 BMP7 null mutation in mice: developmental defects in skeleton, kidney, and eye. Experimental cell research 190 9013703
1998 Recombinant human osteogenic protein-1 (OP-1) stimulates periodontal wound healing in class III furcation defects. Journal of periodontology 173 9526911
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
2003 BMP7 antagonizes TGF-beta -dependent fibrogenesis in mesangial cells. American journal of physiology. Renal physiology 158 12676736
2007 OP-1/BMP-7 in cartilage repair. International orthopaedics 147 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 142 24284793
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
2008 CTGF inhibits BMP-7 signaling in diabetic nephropathy. Journal of the American Society of Nephrology : JASN 116 18632843
1999 Preclinical and clinical evaluation of osteogenic protein-1 (BMP-7) in bony sites. Orthopedics 113 10418861
1997 BMP-2 and OP-1 exert direct and opposite effects on renal branching morphogenesis. The American journal of physiology 107 9435686
2008 BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer letters 102 18980801
2009 BMP7 promotes proliferation of nephron progenitor cells via a JNK-dependent mechanism. Development (Cambridge, England) 98 19793891
2013 BMP7 gene transfer via gold nanoparticles into stroma inhibits corneal fibrosis in vivo. PloS one 93 23799103
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
2012 Bone morphogenetic protein 7 (BMP7) reverses obesity and regulates appetite through a central mTOR pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 85 22331196
1997 Regulation of epidermal induction by BMP2 and BMP7 signaling. Developmental biology 85 9281341
2015 Gremlin1 preferentially binds to bone morphogenetic protein-2 (BMP-2) and BMP-4 over BMP-7. The Biochemical journal 83 25378054
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
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) 77 18446379
2013 BMP7 activates brown adipose tissue and reduces diet-induced obesity only at subthermoneutrality. PloS one 76 24066098
1998 Bone morphogenetic protein-7 (osteogenic protein-1, OP-1) and tooth development. Journal of dental research 74 9539457
2010 Bone morphogenetic protein 7 (BMP7) mutations are associated with variable ocular, brain, ear, palate, and skeletal anomalies. Human mutation 73 20506283
2008 Clinical significance of BMP7 in human colorectal cancer. Annals of surgical oncology 72 18259822
2020 The Role of Bone Morphogenetic Protein 7 (BMP-7) in Inflammation in Heart Diseases. Cells 69 31979268
2019 BMP-7 inhibits renal fibrosis in diabetic nephropathy via miR-21 downregulation. Life sciences 68 31655195
2018 Novel Combination BMP7 and HGF Gene Therapy Instigates Selective Myofibroblast Apoptosis and Reduces Corneal Haze In Vivo. Investigative ophthalmology & visual science 68 29490341
2001 Mutation in Bmp7 exacerbates the phenotype of Bmp8a mutants in spermatogenesis and epididymis. Developmental biology 68 11784057
2008 BMP2 and BMP7 play antagonistic roles in feather induction. Development (Cambridge, England) 66 18635609
2007 Expression of BMP-7 and USAG-1 (a BMP antagonist) in kidney development and injury. Kidney international 66 17943079
2002 Age-related changes in cartilage endogenous osteogenic protein-1 (OP-1). Biochimica et biophysica acta 66 12385776
2002 Osteogenic protein-1 (OP-1, BMP-7) induces osteoblastic cell differentiation of the pluripotent mesenchymal cell line C2C12. Journal of cellular biochemistry 65 12397611
2004 Regulatory role of BMP2 and BMP7 in spermatogonia and Sertoli cell proliferation in the immature mouse. European journal of endocrinology 64 15476453
2017 BMP7-induced-Pten inhibits Akt and prevents renal fibrosis. Biochimica et biophysica acta. Molecular basis of disease 62 28923783
2011 Role of TGF-β and BMP7 in the pathogenesis of oral submucous fibrosis. Growth factors (Chur, Switzerland) 61 21591998
2021 BMP-7 Attenuates Inflammation-Induced Pyroptosis and Improves Cardiac Repair in Diabetic Cardiomyopathy. Cells 60 34685620
2007 FGFR2, FGF8, FGF10 and BMP7 as candidate genes for hypospadias. European journal of human genetics : EJHG 60 17264867
2013 BMP-7 counteracting TGF-beta1 activities in organ fibrosis. Frontiers in bioscience (Landmark edition) 57 23747893
2014 BMP7 drives human adipogenic stem cells into metabolically active beige adipocytes. Lipids 56 25534037
2012 A BMP7 variant inhibits the tumorigenic potential of glioblastoma stem-like cells. Cell death and differentiation 54 22539003
2019 Yin Yang 1 Suppresses Dilated Cardiomyopathy and Cardiac Fibrosis Through Regulation of Bmp7 and Ctgf. Circulation research 52 31495264
2017 BMP7 Induces Uterine Receptivity and Blastocyst Attachment. Endocrinology 52 28324064
2015 BMP-7 Induces Adult Human Pancreatic Exocrine-to-Endocrine Conversion. Diabetes 52 26307584
2018 Sequential BMP7/TGF-β1 signaling and microbiota instruct mucosal Langerhans cell differentiation. The Journal of experimental medicine 50 29343501
1997 OP-1 (BMP-7) affects mRNA expression of type I, II, X collagen, and matrix Gla protein in ossifying long bones in vitro. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 50 9383686
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
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
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
2019 BMP7 functions predominantly as a heterodimer with BMP2 or BMP4 during mammalian embryogenesis. eLife 42 31566563
2014 BMP-7 blocks the effects of TGF-β-induced EMT in cholangiocarcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 40 24969562
1998 Osteogenic protein (OP-1, BMP-7) stimulates cartilage differentiation of human and goat perichondrium tissue in vitro. Journal of biomedical materials research 40 9599038
2008 Bmp7 expression and null phenotype in the urogenital system suggest a role in re-organization of the urethral epithelium. Gene expression patterns : GEP 39 19159697
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
2009 Bone morphogenetic protein 7 (BMP7) gene polymorphisms are associated with inverse relationships between vascular calcification and BMD: the Diabetes Heart Study. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 36 19453255
2003 Modulation of endogenous osteogenic protein-1 (OP-1) by interleukin-1 in adult human articular cartilage. The Journal of bone and joint surgery. American volume 36 12925612
2021 Sulforaphane Ameliorates Diabetes-Induced Renal Fibrosis through Epigenetic Up-Regulation of BMP-7. Diabetes & metabolism journal 35 34082508
2015 BMP4 and BMP7 Suppress StAR and Progesterone Production via ALK3 and SMAD1/5/8-SMAD4 in Human Granulosa-Lutein Cells. Endocrinology 35 26302112
1999 Osteogenic protein-1 (OP-1) blocks cartilage damage caused by fibronectin fragments and promotes repair by enhancing proteoglycan synthesis. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 35 10344470
2019 Differentiating SGBS adipocytes respond to PPARγ stimulation, irisin and BMP7 by functional browning and beige characteristics. Scientific reports 34 30967578
2015 BMP7 reduces inflammation and oxidative stress in diabetic tubulopathy. Clinical science (London, England : 1979) 34 25200314
2013 Theca-derived BMP4 and BMP7 down-regulate connexin43 expression and decrease gap junction intercellular communication activity in immortalized human granulosa cells. The Journal of clinical endocrinology and metabolism 34 23386650
2015 Regulation of α5 and αV Integrin Expression by GDF-5 and BMP-7 in Chondrocyte Differentiation and Osteoarthritis. PloS one 33 26010756
2011 Mechanical loading stimulates BMP7, but not BMP2, production by osteocytes. Calcified tissue international 32 21842277
2021 RIP1 Perturbation Induces Chondrocyte Necroptosis and Promotes Osteoarthritis Pathogenesis via Targeting BMP7. Frontiers in cell and developmental biology 31 33937236
2010 Progesterone decreases bone morphogenetic protein (BMP) 7 expression and BMP7 inhibits decidualization and proliferation in endometrial stromal cells. Human reproduction (Oxford, England) 31 20085912
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
2009 BMP7 and SHH regulate Pax2 in mouse retinal astrocytes by relieving TLX repression. Developmental biology 30 19505455
2019 SPARCL1 promotes C2C12 cell differentiation via BMP7-mediated BMP/TGF-β cell signaling pathway. Cell death & disease 28 31699966
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
2024 BMP7 promotes cardiomyocyte regeneration in zebrafish and adult mice. Cell reports 24 38678558
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 Bmp7 functions via a polarity mechanism to promote cloacal septation. PloS one 24 22253716
2006 In vivo evaluation of plasmid DNA encoding OP-1 protein for spine fusion. Spine 24 16946649

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