ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025
SPP1-ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin-Dependent PINK1/PARKIN Pathway Blockade.
Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed.
- CBX3 aggravates nucleus pulposus cell apoptosis and extracellular matrix degradation in vitro via repressing SESN2-mediated mitophagy in an H3K9me3-dependent manner.Molecular biology reports · 2026Article
- An integrated multi-algorithm analysis to decipher senescence and metabolic characteristics in nucleus pulposus cells during disc degeneration.GeroScience · 2026Article
- Ubiquitination in intervertebral disc degeneration: from mechanisms to potential therapeutic strategies.Journal of orthopaedic translation · 2026Review
- Sestrin2 alleviates age-related hearing loss through mediating PINK1/Parkin related mitophagy.Nagoya journal of medical science · 2026Article
- Single-cell RNA sequencing reveals HMGA2 involvement in neoplastic aggressiveness and endothelial cell senescence in chondrosarcoma.Cell biology and toxicology · 2026Article
- E3 ubiquitin ligases in bone homeostasis: from regulatory mechanisms to skeletal diseases and therapeutic targeting.Frontiers in cell and developmental biology · 2026Review
- Mechanotransduction in intervertebral disc degeneration: from compartment-specific sensors to translational frontiers.Frontiers in bioengineering and biotechnology · 2026Review
- PACS-2 Mitigates NPSC Apoptosis and Intervertebral Disc Degeneration by Preserving MAM Integrity via the SP1/LRRK2/Mfn2 Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- ITGBL1 and RPN1 Mark a Fibrotic NP Subpopulation with Coupled Integrin Signaling and N-Glycosylation Programs in IVDD.Journal of inflammation research · 2026Article
- Single-cell Profiling Reveals Cooperative Participation ofInternational journal of medical sciences · 2026Article
- Succinic Acid-Induced Macrophage Endocytosis Promotes Extracellular Vesicle-Based Integrin Beta1 Transfer Accelerating Fibroblast Activation and Sepsis-Associated Pulmonary Fibrosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Negative Correlation Between Secreted Phosphoprotein 1 and the Treg/Th17 Ratio in Non-Valvular Atrial Fibrillation.Reviews in cardiovascular medicine · 2025Article
- Immunoinflammation and post-translational modifications in the aging process.Journal of translational medicine · 2025Review
- Nerve growth factor-loaded biomimetic prussian blue nanocomplexes for reversing osteoporosis via promoting osteoblast precursor cell proliferation and differentiation.Materials today. Bio · 2025Article
- SPP1-ITGα5/β1 Accelerates Calcification of Nucleus Pulposus Cells by Inhibiting Mitophagy via Ubiquitin-Dependent PINK1/PARKIN Pathway Blockade.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Region-specific mitophagy in nucleus pulposus, annulus fibrosus, and cartilage endplate of intervertebral disc degeneration: mechanisms and therapeutic strategies.Frontiers in pharmacology · 2025Review
Corrections and comments
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Authors and funding
12 authors.
Funding
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.
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