ArticleAging cell2020
Transformation of resident notochord-descendent nucleus pulposus cells in mouse injury-induced fibrotic intervertebral discs.
Article in Aging cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- Versatile Microgel Platform for Intervertebral Disc Degeneration Therapy: Targeting Pericyte-Mediated Fibrosis and Protecting Nucleus Pulposus Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Intervertebral disc progenitor cells: roles in regeneration and disease.Stem cell research & therapy · 2026Review
- Dual-Lineage Chondrocyte-Like Cells in the Nucleus Pulposus of Aging Intervertebral Discs Are Accelerated by Hedgehog Signaling Inactivation.Aging cell · 2025Article
- What a pain in the back: etiology, diagnosis and future treatment directions for discogenic low back pain.Bone research · 2025Review
- Human iPSCs Derived MSCs-Secreted Exosomes Modulate Senescent Nucleus Pulposus Cells Induced Macrophage Polarization via Metabolic Reprogramming to Mitigate Intervertebral Disc Degeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Upregulated CEMIP promotes intervertebral disc degeneration via AP-1-mediated change in chromatin accessibility.Clinical and translational medicine · 2025Article
- Article
- Nanomedicine Approaches for Intervertebral Disc Regeneration: From Bench to Bedside.Pharmaceutics · 2025Review
- Biglycan fragment modulates TGF-β activity in intervertebral disc via an eIF6-coupled intracellular path.Science advances · 2025Article
- Fibrocyte enrichment and myofibroblastic adaptation causes nucleus pulposus fibrosis and associates with disc degeneration severity.Bone research · 2025Article
- Nano-Drug Delivery System Targeting the Oxidative Stress Microenvironment: A Prospective Strategy for Intervertebral Disc Degeneration Treatment.International journal of nanomedicine · 2025Review
- An anti-FAP-scFv-functionalized exosome-carrying hydrogel deliversTheranostics · 2025Article
- Dedifferentiation-like reprogramming of degenerative nucleus pulposus cells into notochordal-like cells by defined factors.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Characterization of the Nucleus Pulposus Progenitor Cells via Spatial Transcriptomics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Machine learning algorithm predicts fibrosis-related blood diagnosis markers of intervertebral disc degeneration.BMC medical genomics · 2023Article
- Physalin A alleviates intervertebral disc degeneration via anti-inflammatory and anti-fibrotic effects.Journal of orthopaedic translation · 2023Article
- Intervertebral disc degeneration and osteoarthritis: a common molecular disease spectrum.Nature reviews. Rheumatology · 2023Review
- Controversies in spine research: Organ culture versus in vivo models for studies of the intervertebral disc.JOR spine · 2022Review
- Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intervertebral disc degeneration (IDD), a major cause of low back pain, occurs with ageing. The core of the intervertebral disc, the nucleus pulposus (NP), embedded in a proteoglycan-rich and gelatinous matrix, is derived from the embryonic notochord. With IDD, the NP becomes fibrous, containing fewer cells, which are fibroblastic and of unknown origin. Here, we used a lineage tracing strategy to investigate the origin of cells in the NP in injury-induced mouse IDD. We established a Foxa2 notochord-specific enhancer-driven Cre transgenic mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). When this mouse is crossed to one carrying a Cre recombinase reporter, Z/EG, EGFP-labelled NP cells are present even at 2 years of age, consistent with their notochordal origin. We induced tail IDD in Foxa2mNE-Cre; Z/EG mice by annulus puncture and observed the degenerative changes for 12 weeks. Soon after puncture, EGFP-labelled NP cells showed strong Col2a1+ expression unlike uninjured control NP. Later, accompanying fibrotic changes, EGFP-positive NP cells expressed fibroblastic and myofibroblastic markers such as Col1a1, ASMA, FAPA and FSP-1. The number of EGFP+ cells co-expressing the fibroblastic markers increased with time after puncture. Our findings suggest resident NP cells initially upregulate Col2a1+ and later transform into fibroblast-like cells during injury-mediated disc degeneration and remodelling. This important discovery concerning the cellular origin of fibrotic pathology in injury-induced IDD has implications for management in disease and ageing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.