BMP7 Gene (Bone Morphogenetic Protein 7)
Overview
<div class="infobox infobox-gene">
<h3>BMP7</h3>
<table>
<tr><th>Symbol</th><td>BMP7</td></tr>
<tr><th>Full Name</th><td>Bone Morphogenetic Protein 7</td></tr>
<tr><th>Chromosomal Location</th><td>20q12</td></tr>
<tr><th>NCBI Gene ID</th><td>[656](https://www.ncbi.nlm.nih.gov/gene/656)</td></tr>
<tr><th>OMIM</th><td>[157255](https://www.omim.org/entry/157255)</td></tr>
<tr><th>Ensembl ID</th><td>[ENSG00000101144](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101144)</td></tr>
<tr><th>UniProt</th><td>[P18075](https://www.uniprot.org/uniprot/P18075)</td></tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/alzheimer-disease" style="color:#ef9a9a">ALZHEIMER DISEASE</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">Alzheimer</a>, <a href="/wiki/autoimmune" style="color:#ef9a9a">Autoimmune</a>, <a href="/wiki/cancer" style="color:#ef9a9a">Cancer</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">63 edges</a></td>
</tr>
</table>
</div>
BMP7 (Bone Morphogenetic Protein 7), also known as osteogenic protein-1 (OP-1), encodes a member of the [TGF-beta superfamily](/mechanisms/tgf-beta-signaling) of signaling molecules. BMP7 is widely expressed in adult tissues and has important roles in bone formation, kidney development, tissue repair, and neuroprotection. In the nervous system, BMP7 has demonstrated significant neuroprotective properties, making it a promising therapeutic candidate for [Alzheimer's Disease](/diseases/alzheimers-disease) and [Parkinson's Disease](/diseases/parkinsons-disease)[@chen2014].
Unlike BMP4, which tends to promote astrocyte differentiation, BMP7 has more neuroroprotective effects and promotes neuronal survival across multiple models of neurodegeneration.
Protein Structure and Function
TGF-beta Superfamily Structure
BMP7 shares the characteristic TGF-beta superfamily architecture:
- Precursor protein: ~431 amino acids
- Signal peptide: N-terminal targeting sequence
- Prodomain: Removed during processing
- Mature dimer: Active form (~115 amino acids per monomer)
The mature BMP7 forms:
- Homodimers: Most common active form
- Heterodimers: Can pair with BMP2 or BMP4 for enhanced activity
- Disulfide bonds: Cysteine-mediated dimerization
Receptor Interactions
BMP7 signals through similar receptors to BMP4:
Type I Receptors:
- BMPR1A (ALK3): Widely expressed
- BMPR1B (ALK6): More restricted expression
Type II Receptor:
- BMPR2: Constitutively active
- ACTR2 (ActRII): Can also mediate BMP7 signals
Alternative Receptors:
- BMP7 can also signal through activin type II receptors
- Provides tissue-specific effects
Signaling Pathways
BMP7 activates multiple intracellular pathways:
SMAD-Dependent:
- Phosphorylates SMAD1/5/8
- Forms complexes with SMAD4
- Transcriptional regulation
SMAD-Independent:
- MAPK pathways (ERK, p38, JNK)
- PI3K/AKT pathway
- Provides non-genomic effects
Neuroprotective Mechanisms
Anti-Apoptotic Effects
BMP7 exerts potent anti-apoptotic effects[@yoon2006]:
Caspase Inhibition:
- Reduces caspase-3 activation
- Blocks mitochondrial apoptosis pathway
- Preserves neuronal viability
Bcl-2 Family Modulation:
- Increases Bcl-2 expression
- Reduces Bax translocation
- Maintains mitochondrial integrity
AKT Pathway Activation:
- Activates pro-survival AKT signaling
- Phosphorylates BAD
- Promotes cell survival
Anti-Inflammatory Effects
BMP7 modulates neuroinflammation[@uchiyama2019]:
Microglial Activation:
- Reduces pro-inflammatory cytokine production
- Modulates microglial phenotype
- Promotes anti-inflammatory state
Astrocyte Regulation:
- Modulates astrocytic responses
- Reduces reactive gliosis
- Maintains homeostatic functions
Cytokine Modulation:
- Reduces TNF-α, IL-1β, IL-6
- Increases anti-inflammatory mediators
Anti-Amyloid Effects
BMP7 affects amyloid pathology[@yang2016]:
APP Processing:
- Modulates secretase activity
- May reduce amyloid-beta production
Amyloid Clearance:
- Promotes clearance mechanisms
- Enhances microglial phagocytosis
Tau Pathology:
- Reduces tau hyperphosphorylation
- Protects against NFT formation
Role in Alzheimer's Disease
Amyloid Pathology
BMP7 has several beneficial effects on amyloid pathology:
Reduced Amyloid-beta Production:
- Modulates α- and β-secretase activity
- Shifts processing toward non-amyloidogenic pathway
Enhanced Clearance:
- Promotes microglial phagocytosis
- Increases extracellular proteolysis
Neuroprotection Against Amyloid:
- Protects neurons from amyloid toxicity
- Preserves synaptic function
Tau Pathology
BMP7 addresses tau pathology[@yang2016]:
Reduces Hyperphosphorylation:
- Modulates GSK-3β activity
- Reduces tau kinase activation
Prevents Aggregation:
- Maintains tau solubility
- Protects against NFT formation
Synaptic Function
BMP7 protects synaptic elements:
- Preserves dendritic spines
- Maintains synaptic plasticity
- Improves cognitive function
Role in Parkinson's Disease
Dopaminergic Neuron Protection
BMP7 is particularly important for dopaminergic neurons[@deptala2003]:
Development:
- Essential for dopaminergic neuron specification
- Promotes differentiation of dopaminergic lineage
Survival:
- Protects dopaminergic neurons from toxins
- Supports mitochondrial function
Regeneration:
- Promotes dopaminergic neuron survival
- May support regeneration approaches
MPTP and 6-OHDA Models
In toxin-based PD models:
- BMP7 protects against MPTP toxicity
- Reduces dopaminergic neuron loss
- Improves behavioral outcomes
Neuroinflammation
BMP7 modulates PD-related inflammation:
- Reduces microglial activation
- Decreases pro-inflammatory cytokines
- Protects neurons from inflammation-mediated damage
Role in Kidney Disease
BMP7 has significant renoprotective effects[@vukicevic2008]:
Nephrogenesis:
- Critical for kidney development
- Promotes ureteric bud branching
Adult Kidney:
- Maintains tubular cell function
- Protects against fibrosis
Disease Applications:
- Diabetic nephropathy
- Acute kidney injury
- Chronic kidney disease
This is relevant to neurodegeneration because kidney dysfunction is a common comorbidity in AD/PD patients.
Expression Patterns
Tissue Distribution
BMP7 is expressed in:
- Bone and cartilage: Original discovery context
- Kidney: High expression in adult
- Brain: Cortex, hippocampus, cerebellum
- Heart: Lower expression
- Lung: Moderate expression
Brain Region Expression
In the brain:
- Cortex: Pyramidal neurons
- Hippocampus: CA1, CA3, dentate gyrus
- Cerebellum: Purkinje cells
- Substantia nigra: Dopaminergic neurons
- Hypothalamus: Various nuclei
Cellular Localization
BMP7 is produced by:
- Neurons: Both excitatory and inhibitory
- Astrocytes: Astrocytic expression
- Oligodendrocytes: Myelinating cells
Therapeutic Implications
Preclinical Results
BMP7 has shown promise in multiple models:
AD Models:
- Improved cognitive function
- Reduced amyloid burden
- Decreased tau pathology
PD Models:
- Protected dopaminergic neurons
- Improved motor function
- Reduced neuroinflammation
Delivery Approaches
Several delivery strategies are being explored:
Protein Delivery:
- Recombinant BMP7 protein
- Direct injection or infusion
Gene Therapy:
- AAV-mediated BMP7 expression
- Viral delivery to specific brain regions
Small Molecules:
- BMP7 receptor agonists
- Mimetic peptides
Clinical Considerations
- BMP7 has been used clinically for bone healing
- CNS delivery challenges remain
- Dose and timing critical for effects
- Combination therapies may be optimal
Key Research Findings
2018-2024 Research Highlights
Neuroinflammation: BMP7's anti-inflammatory effects are increasingly characterized.
Tau Pathology: Direct effects on tau pathology validated in multiple models.
Combination Therapy: BMP7 with other growth factors shows enhanced effects.
Delivery Advances: Improved delivery methods for CNS application.Mermaid diagram (expand to render)
Cross-Links to Related Pages
- [TGF-beta signaling](/mechanisms/tgf-beta-signaling)
- [BMP signaling](/mechanisms/bmp-signaling)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Parkinson's Disease](/diseases/parkinsons-disease)
- [Kidney disease](/diseases/kidney-disease)
- [Neuroprotection](/mechanisms/neuroprotection)
- [Dopaminergic neurons](/entities/dopaminergic-neurons)
- [Amyloid-beta](/proteins/amyloid-beta)
- [Tau protein](/proteins/tau-protein)
- [SMAD proteins](/proteins/smad-proteins)
References
[Deptala et al., BMP-7: a neurotrophic factor for dopaminergic neurons (2003)](https://doi.org/10.1007/s00702-003-0032-8)
[Yoon et al., BMP7 ameliorates amyloid-beta-induced cognitive deficits (2006)](https://doi.org/10.1016/j.nbd.2006.07.015)
[Leonard et al., BMP7 protects dopaminergic neurons from MPTP toxicity (2009)](https://doi.org/10.1016/j.neuropharm.2009.08.010)
[Chen et al., BMPs in neurodegenerative diseases (2014)](https://doi.org/10.1007/s12035-014-8741-4)
[Vukicevic et al., BMP-7: a bone-forming factor in kidney (2008)](https://doi.org/10.1038/ki.2008.516)
[Zhang et al., BMP-7 prevents glial activation (2009)](https://doi.org/10.1016/j.brainres.2009.06.057)
[Stott & Barker, BMP7 expression in Parkinson's disease (2010)](https://doi.org/10.1007/s00702-010-0452-1)
[Hu et al., Therapeutic potential of BMP7 in neurodegenerative diseases (2019)](https://doi.org/10.2174/1567205016666190806153944)
[Uchiyama et al., BMP7 regulates astrogliosis in AD (2019)](https://doi.org/10.1186/s12974-019-1590-5)
[Yang et al., BMP7 attenuates tau hyperphosphorylation (2016)](https://doi.org/10.3233/JAD-160354)
[Abdel Aziz et al., BMP7 reduces neuroinflammation in AD (2018)](https://doi.org/10.1007/s11064-018-2620-8)External Links
- [NCBI Gene: 656](https://www.ncbi.nlm.nih.gov/gene/656)
- [OMIM: 157255](https://www.omim.org/entry/157255)
- [Ensembl: ENSG00000101144](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000101144)
- [UniProt: P18075](https://www.uniprot.org/uniprot/P18075)
- [GeneCards: BMP7](https://www.genecards.org/cgi-bin/carddisp.pl?gene=BMP7)
Pathway Diagram
The following diagram shows the key molecular relationships involving BMP7 Gene (Bone Morphogenetic Protein 7) discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)