gene

SPP1

Entity Detail — Knowledge Graph Node

Understanding Entity Pages

This page aggregates everything SciDEX knows about SPP1: its mechanistic relationships (Knowledge Graph edges), hypotheses targeting it, analyses mentioning it, and supporting scientific papers. The interactive graph below shows its immediate neighbors. All content is AI-synthesized from peer-reviewed literature.

446Connections

22Hypotheses

5Analyses

50Outgoing

50Incoming

5Experiments

5Debates

Summary

SPP1 encodes osteopontin, a matricellular protein involved in neuroinflammation, cell survival, and neurodegenerative disease pathogenesis

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🧬 Gene Info

Gene Symbol	Secreted Phosphoprotein 1 (Osteopontin)
Chromosome	4q21.1
Function	encodes a secreted matricellular glycoprotein that functions as a cytokine, chemokine, and extracellular matrix protein.
Amino Acids	314 aa
Pathways	Amyloid, Angiogenesis, Apoptosis, Complement, Immune Response
UniProt ID	P08421
NCBI Gene ID	6696
Ensembl ID	ENSG00000118733
OMIM	166490
Associated Diseases	AD, Als, Alzheimer, Alzheimer's disease, Cancer, Carcinoma
Known Drugs/Compounds	amyloid-beta oligomers, Bap, BaP, rapamycin, ursolic acid
Interactions	ABCA1, Actin, Akt, AKT, ALZHEIMER, ALZHEIMER'S DISEASE
SciDEX Hypotheses	Temporal SPP1 Inhibition During Critical Windows PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Medi LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to I (+11 more)
KG Connections	446 knowledge graph edges
Databases	GeneCards HPA STRING

🔮 Predicted Structure: SPP1 — AlphaFold P08421 Click to expand

AI-predicted structure from AlphaFold | Powered by Mol*

Wiki Pages (2)

Knowledge base pages for this entity

Canonical Page

SPP1 Gene

gene · 1494 words

→

Osteopontin (SPP1)

protein · 2490 words

→

Pathway Diagram

graph TD
    SPP1["SPP1/Osteopontin
Matricellular Protein"] -->|"activates"| C1QA["C1QA/Complement"]
    SPP1 -->|"activates"| Complement["Complement System"]
    SPP1 -->|"activates"| GRN["GRN/Progranulin"]
    SPP1 -->|"activates"| CTSB["CTSB"]
    SPP1 -->|"activates"| Amyloid["Amyloid Pathology"]

    SPP1 -->|"inhibits"| Angiogenesis["Angiogenesis"]
    SPP1 -->|"expressed in"| Myeloid["Myeloid Cells"]

    CHI3L1["CHI3L1"] -->|"regulates"| SPP1
    GBM["GBM"] -->|"activates"| SPP1
    ICAM1["ICAM1"] -->|"inhibits"| SPP1
    MMP9["MMP9"] -->|"inhibits"| SPP1

    SPP1 -->|"implicated in"| AD["Alzheimer's Disease"]
    SPP1 -->|"implicated in"| ALS["ALS"]
    SPP1 -->|"activates"| Dementia["Dementia"]
    SPP1 -->|"regulates"| Glioblastoma["Glioblastoma"]
    SPP1 -->|"therapeutic target"| Inflammation["Neuroinflammation"]

    style SPP1 fill:#e74c3c,stroke:#c0392b,color:#e0e0e0
    style C1QA fill:#3498db,stroke:#2980b9,color:#e0e0e0
    style Complement fill:#3498db,stroke:#2980b9,color:#e0e0e0
    style AD fill:#9b59b6,stroke:#8e44ad,color:#e0e0e0
    style ALS fill:#9b59b6,stroke:#8e44ad,color:#e0e0e0
    style Inflammation fill:#f39c12,stroke:#e67e22,color:#e0e0e0

Outgoing (281)

Target	Relation	Type	Str
Microglial Phagocytosis	promotes	process	0.95
Macrophage Inflammation	promotes	process	0.95
Lipid Dysregulation	promotes	phenotype	0.95
Microglial Phagocytic States	associated_with	process	0.95
Synaptic Engulfment	mediates	process	0.95
Th17 cell differentiation	promotes	process	0.95
ALZHEIMER'S DISEASE	involved_in	disease	0.95
Microglial Phagocytosis	activates	process	0.95
Atherosclerosis	contributes_to	disease	0.95
microglial phagocytosis	drives	process	0.95
SYNAPTIC ENGULFMENT	mediates	entity	0.95
PHAGOCYTOSIS	regulates	entity	0.95
ALZHEIMER'S DISEASE	implicated_in	entity	0.95
ITGB1	binds_to	protein	0.93
CD44	binds_to	protein	0.93
microglial phagocytic state	associated_with	phenotype	0.93
synaptic engulfment	promotes	process	0.92
ERK	activates	protein	0.92
Microglia	associated_with	cell_type	0.92
macrophage inflammation	promotes	process	0.90
GRN	upregulates	gene	0.90
microglia	induces	cell_type	0.90
C1QA	upregulates	gene	0.90
CTSB	upregulates	gene	0.90
HIPPOCAMPUS	expressed_in	entity	0.90
Inflammation	promotes	process	0.90
C1Q	upregulates	entity	0.90
Synaptic Loss	contributes_to	phenotype	0.90
MICROGLIA	mediates	cell_type	0.90
PI3K/Akt/mTOR pathway	activates	pathway	0.90
idiopathic pulmonary fibrosis	causes	disease	0.90
NSCLC	causes	disease	0.90
Phagocytic Markers	upregulates	biomarker	0.90
Microglial Phagocytosis	upregulates	process	0.88
Alzheimer's Disease	therapeutic_target	disease	0.88
Macrophage Cytotoxicity	mediates	phenotype	0.85
lipid dysregulation	mediates	phenotype	0.85
Alzheimer'S Disease	involved_in	disease	0.85
MICROGLIA	associated_with	cell_type	0.80
phagocytic_state	induces	biological_process	0.80
foam cell phenotype	promotes	phenotype	0.80
atherosclerosis	therapeutic_target	disease	0.80
Senescence	activates	disease	0.75
ABCA1	suppresses	gene	0.75
CD36	upregulates	gene	0.75
PLIN2	upregulates	gene	0.75
neurons	expressed_in	cell_type	0.70
glioma cell	activates	cell_type	0.70
RAGE	therapeutic_target	gene	0.70
microglia	expressed_in	cell_type	0.70

Incoming (165)

Source	Relation	Type	Str
h-immunity-03dc171e	relates_to	hypothesis	0.00
Bap	upregulates	compound	0.95
Mir-692	inhibits	biomarker	0.95
PERIVASCULAR MACROPHAGES	expressed_in	entity	0.95
BaP	upregulates	compound	0.95
ursolic acid	inhibits	drug	0.91
PERIVASCULAR FIBROBLASTS	expressed_in	entity	0.90
perivascular_cells	upregulates	cell_type	0.90
Bap	binds	compound	0.90
Perivascular Macrophages	upregulates	cell_type	0.90
Perivascular Fibroblasts	upregulates	cell_type	0.85
BaP	binds	compound	0.85
Perivascular Cells	expressed_in	cell_type	0.85
amyloid-beta oligomers	modulates	compound	0.80
MICROGLIA	associated_with	cell_type	0.80
RPS18	co_expressed_with	gene	0.80
COL1A1	associated_with	gene	0.60
THBS2	associated_with	gene	0.60
STAT3	regulates	gene	0.60
MMP3	associated_with	gene	0.60
APOE	associated_with	gene	0.60
YBX1	activates	gene	0.60
ANXA2	activates	gene	0.60
ICAM1	activates	gene	0.60
CD44	activates	gene	0.60
HMOX1	activates	gene	0.60
LGALS3	associated_with	gene	0.60
PI3K	associated_with	gene	0.60
FGF19	associated_with	gene	0.60
PLAU	associated_with	gene	0.60
AKT	associated_with	gene	0.60
TNF	associated_with	gene	0.60
NME1	associated_with	gene	0.60
HSP90AA1	associated_with	gene	0.60
PINK1	inhibits	gene	0.60
C1QA	regulates	entity	0.60
CTSB	regulates	entity	0.60
GRN	regulates	entity	0.60
BLM	activates	gene	0.60
AKT	activates	gene	0.60
CANCER	associated_with	gene	0.60
RNA	associated_with	gene	0.60
CAMK4	associated_with	gene	0.60
CD8	associated_with	gene	0.60
RB1	therapeutic_target	gene	0.60
CHI3L1	regulates	gene	0.60
GBM	activates	gene	0.60
ANK3	associated_with	gene	0.60
ERK	associated_with	gene	0.60
CANCER	therapeutic_target	gene	0.60

Targeting Hypotheses (22)

Hypotheses where this entity is a therapeutic target

Hypothesis	Score	Disease	Analysis
Temporal SPP1 Inhibition During Critical Windows	0.728	neuroinflammation	What molecular mechanisms mediate SPP1-i
TREM2-Dependent Switch Hypothesis: TREM2 Agonism Redirects S	0.708	synaptic biology	Does SPP1-mediated synaptic engulfment r
SPP1+ DAM as Source of Autoimmunity in Neurodegeneration	0.660	Alzheimer's disease	-
Metabolic Rewiring via SPP1-Induced HIF1α Glycolytic Shift	0.620	neuroinflammation	What molecular mechanisms mediate SPP1-i
PDGF-BB/PDGFRβ/STAT3 Paracrine Signaling Axis Mediates Aβ-In	0.618	neurodegeneration	How do perivascular cells specifically r

Complement Cascade Specificity: Microglial C3aR Antagonism D	0.618	synaptic biology	Does SPP1-mediated synaptic engulfment r
LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasom	0.617	neurodegeneration	How do perivascular cells specifically r
Temporal NLRP3 Inhibition During SPP1-Driven Microglial Acti	0.551	neuroinflammation	What molecular mechanisms mediate SPP1-i
Astrocytic SPP1 Modulation Through STAT3-Dependent Transcrip	0.551	neuroinflammation	What molecular mechanisms mediate SPP1-i
Synaptic Vulnerability Window Temporal Targeting: Transient	0.540	synaptic biology	Does SPP1-mediated synaptic engulfment r
CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macr	0.535	neurodegeneration	How do perivascular cells specifically r
Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement F	0.518	synaptic biology	Does SPP1-mediated synaptic engulfment r
TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1	0.496	neurodegeneration	How do perivascular cells specifically r
Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhanc	0.496	neuroinflammation	What molecular mechanisms mediate SPP1-i
YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1	0.492	neurodegeneration	How do perivascular cells specifically r
Source-Specific SPP1 Inhibition: Perivascular Cell Targeting	0.466	synaptic biology	Does SPP1-mediated synaptic engulfment r
Astrocytic SPP1 Modulation via STAT3-Dependent Transcription	0.459	neuroinflammation	What molecular mechanisms mediate SPP1-i
Mitochondrial Damage-Triggered SPP1 Inflammasome Coupling	0.453	neuroinflammation	What molecular mechanisms mediate SPP1-i
Astrocytic SPP1 Modulation for Neuroinflammatory Resolution	0.447	neuroinflammation	What molecular mechanisms mediate SPP1-i
RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upre	0.442	neurodegeneration	How do perivascular cells specifically r
P2X7/P2Y12 Purinergic Signaling Connects Aβ Aggregation to S	0.423	neurodegeneration	How do perivascular cells specifically r
Partial Agonist/SPP1 Splice Variant Strategy: Splice-Switchi	0.375	synaptic biology	Does SPP1-mediated synaptic engulfment r

Mentioning Analyses (5)

Scientific analyses that reference this entity

What molecular mechanisms mediate SPP1-induced microglial phagocytic activation

neuroinflammation | 2026-04-15 | 7 hypotheses Top: 0.728

Does SPP1-mediated synaptic engulfment represent beneficial clearance or patholo

synaptic biology | 2026-04-07 | 7 hypotheses Top: 0.708

How do perivascular cells specifically recognize and respond to amyloid-β to upr

neurodegeneration | 2026-04-06 | 7 hypotheses Top: 0.618

What molecular mechanisms mediate SPP1-induced microglial phagocytic activation

neuroinflammation | 2026-04-06 | 7 hypotheses Top: 0.730

Immune atlas neuroinflammation analysis in neurodegeneration

Neuroinflammation | 2026-04-03 | 4 hypotheses Top: 0.646

Experiments (5)

Experimental studies targeting or related to this entity

Experiment	Type	Disease	Score	Model	Status	Est. Cost
SPP1-mediated microglial synaptic engulfment assay	exploratory	Alzheimer's disease	0.950	AD mouse models with amyloid-β	proposed	N/A
SPP1 upregulation in perivascular cells in AD mouse models	exploratory	Alzheimer's disease	0.900	AD mouse models	proposed	N/A
Spp1 knockout prevents synaptic loss in AD mouse models	validation	Alzheimer's disease	0.900	Spp1 knockout AD mouse models	proposed	N/A
Single-cell RNA sequencing of microglial states in AD hippocampus	exploratory	Alzheimer's disease	0.850	AD mouse hippocampus	proposed	N/A
Cell-cell interaction analysis of perivascular-microglial crosstalk	exploratory	Alzheimer's disease	0.800	AD mouse models	proposed	N/A

Related Papers (0)

Scientific publications cited in analyses involving this entity

Title & PMID	Authors	Journal	Year	Citations
No papers found

Debates (5)

Multi-agent debates referencing this entity

The study shows SPP1 from perivascular cells drives microglial synaptic engulfme

closed · Rounds: 4 · Score: 0.70 · 2026-04-22

The abstract indicates SPP1 upregulation occurs in perivascular macrophages and

closed · Rounds: 4 · Score: 0.67 · 2026-04-22

While SPP1 absence prevents synaptic loss, it's unclear whether this represents

closed · Rounds: 4 · Score: 0.69 · 2026-04-21

What molecular mechanisms mediate SPP1-induced microglial phagocytic activation

closed · Rounds: 5 · Score: 0.95 · 2026-04-15

Comprehensive analysis of immune cell subtypes in neurodegeneration: microglia s

closed · Rounds: 4 · Score: 0.85 · 2026-04-03

Related Research

Hypotheses and analyses mentioning SPP1 in their description or question text

Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1

Score: 0.618 · synaptic biology · 2026-04-21

## Mechanistic Overview Complement Cascade Specificity: Microglial C3aR Antagonism Downstream of SPP1 starts from the cl

LRP1/NLRP3/IL-1β Cascade Links Aβ Endocytosis to Inflammasome Activation and SPP

Score: 0.617 · neurodegeneration · 2026-04-22

**Molecular Mechanism and Rationale** The proposed LRP1/NLRP3/IL-1β cascade represents a critical mechanistic link betw

Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation Windows

Score: 0.551 · neuroinflammation · 2026-04-20

## Mechanistic Overview Temporal NLRP3 Inhibition During SPP1-Driven Microglial Activation Windows starts from the claim

Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional Control

Score: 0.551 · neuroinflammation · 2026-04-20

## Mechanistic Overview Astrocytic SPP1 Modulation Through STAT3-Dependent Transcriptional Control starts from the claim

Synaptic Vulnerability Window Temporal Targeting: Transient SPP1 Blockade

Score: 0.540 · synaptic biology · 2026-04-21

## Mechanistic Overview Synaptic Vulnerability Window Temporal Targeting: Transient SPP1 Blockade starts from the claim

CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering

Score: 0.535 · neurodegeneration · 2026-04-22

## Mechanistic Overview CD36 Acts as Primary Aβ Oligomer Sensor on Perivascular Macrophages, Triggering NF-κB-Dependent

Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late Inhi

Score: 0.518 · synaptic biology · 2026-04-21

## Mechanistic Overview Stage-Dependent Biphasic SPP1 Targeting: Early Enhancement Followed by Late Inhibition starts fr

TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through

Score: 0.496 · neurodegeneration · 2026-04-22

## Mechanistic Overview TREM2 on Perivascular Macrophages Senses Aβ and Drives SPP1 Upregulation Through CSF1R-Mediated

Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critica

Score: 0.496 · neuroinflammation · 2026-04-21

## Mechanistic Overview Temporal NLRP3 Inhibition via SPP1-Mediated Mitophagy Enhancement During Critical Neuroinflammat

YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Pe

Score: 0.492 · neurodegeneration · 2026-04-22

## Mechanistic Overview YAP/TAZ Mechanosensing Cooperates with NF-κB to Amplify SPP1 Transcription in Perivascular Fibro

Source-Specific SPP1 Inhibition: Perivascular Cell Targeting

Score: 0.466 · synaptic biology · 2026-04-21

## Mechanistic Overview Source-Specific SPP1 Inhibition: Perivascular Cell Targeting starts from the claim that modulati

Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional Control

Score: 0.459 · neuroinflammation · 2026-04-21

## Mechanistic Overview Astrocytic SPP1 Modulation via STAT3-Dependent Transcriptional Control starts from the claim tha

Mitochondrial Damage-Triggered SPP1 Inflammasome Coupling

Score: 0.453 · neuroinflammation · 2026-04-21

## Mechanistic Overview Mitochondrial Damage-Triggered SPP1 Inflammasome Coupling starts from the claim that modulating

Astrocytic SPP1 Modulation for Neuroinflammatory Resolution

Score: 0.447 · neuroinflammation · 2026-04-21

## Mechanistic Overview Astrocytic SPP1 Modulation for Neuroinflammatory Resolution starts from the claim that modulatin

RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivasc

Score: 0.442 · neurodegeneration · 2026-04-22

## Mechanistic Overview RAGE/STAT3/IL-6 Autocrine Loop Mediates Aβ-Induced SPP1 Upregulation in Perivascular Fibroblasts