CDB15:0001406 SPP1 — ITGA5

Experimentally validated in Human, Rat; Orthology-inferred in Human, Mouse, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep, Rat

Title

Journal:; Year Published:

Abstract

SPP1-ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin-Dependent PINK1/PARKIN Pathway Blockade.

Advanced science, 2025; PubMed, Homo sapiens SPP1 — Homo sapiens ITGA5

ABSTRACT: Low back pain (LBP) caused by nucleus pulposus degeneration and calcification leads to great economic and social burden worldwide. Unexpectedly, no previous studies have demonstrated the association and the underlying mechanism between nucleus pulposus tissue degeneration and calcification formation. Secreted Phosphoprotein 1 (SPP1) exerts crucial functions in bone matrix mineralization and calcium deposition. Here, a novel function of SPP1 is reported, namely that it can aggravate nucleus pulposus cells (NPs) degeneration by negatively regulating extracellular matrix homeostasis. The degenerated NPs have a higher mineralization potential, which is achieved by SPP1. Mechanistically, SPP1 can accelerate the degeneration of nucleus pulposus cells by activating integrin α5β1 (ITGα5/β1), aggravating mitochondrial damage and inhibiting mitophagy. SPP1-ITGα5/β1 axis inhibits mitophagy by PINK1/PARKIN pathway blockade. In conclusion, SPP1 activates ITGα5/β1 to inhibit mitophagy, accelerates NPs degeneration, and induces calcification, thereby leading to intervertebral disc degeneration (IVDD) and calcification, identifying the potentially unknown mechanism and relationship between IVDD and calcification. Important insights are provided into the role of SPP1 in nucleus pulposus calcification in IVDD by inducing nucleus pulposus cell senescence through inhibition of mitophagy and may help develop potential new strategies for IVDD treatment.

Basic Information on SPP1

Ligand Name: secreted phosphoprotein 1

Other Symbols: BNSP, OPN, BSPI, ETA-1, lnc-PKD2-2-3

Ligand Location: secreted based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: SPP1

GeneCards: SPP1

HGNC Gene Group: Secretory calcium-binding phosphoprotein family, Receptor ligands

Functional Annotations for SPP1

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for SPP1

SPP1 — CD44 ・ SPP1 — ITGA4 ・ SPP1 — ITGA9 ・ SPP1 — ITGAV ・ SPP1 — ITGB1 ・ SPP1 — ITGB3 ・ SPP1 — ITGB5 ・ SPP1 — ITGA8 ・ SPP1 — ITGB6

Basic Information on ITGA5

Receptor Name: integrin subunit alpha 5

Other Symbols: FNRA, CD49e

Receptor Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: ITGA5

GeneCards: ITGA5

HGNC Gene Group: CD molecules, Integrins

Functional Annotations for ITGA5

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for ITGA5

ADAM15 — ITGA5 ・ ADAM17 — ITGA5 ・ ANGPT1 — ITGA5 ・ COL18A1 — ITGA5 ・ CCN2 — ITGA5 ・ FBN1 — ITGA5 ・ FGA — ITGA5 ・ FN1 — ITGA5 ・ L1CAM — ITGA5 ・ VTN — ITGA5 ・ ANGPTL2 — ITGA5 ・ CCN4 — ITGA5 ・ CXCL12 — ITGA5 ・ PLA2G2A — ITGA5 ・ SPON2 — ITGA5 ・ AGGF1 — ITGA5 ・ ANGPT2 — ITGA5 ・ ANGPTL4 — ITGA5 ・ CCN3 — ITGA5 ・ CD40LG — ITGA5 ・ COL4A3 — ITGA5 ・ IL1B — ITGA5 ・ MIA — ITGA5 ・ TGM2 — ITGA5 ・ THBS4 — ITGA5 ・ THY1 — ITGA5