Dataset Information

Transcriptomic evaluation of ovine intervertebral disc cells as an in vitro model to explore degenerative processes

ABSTRACT: Intervertebral disc degeneration (IVDD) is a leading cause of chronic back pain and disability. Understanding the cellular and molecular mechanisms underlying disc degeneration is crucial for developing effective therapies. This study investigates the relevance of a cellular model using annulus fibrosus (AF) and nucleus pulposus (NP) cells isolated from lamb and aged sheep discs. Histological analysis and MRI were used to confirm moderate degeneration in 7–8-year-old sheep discs. High-throughput RNA sequencing (RNAseq) was performed on four samples per condition: AF lamb, NP lamb, AF sheep, and NP sheep. Transcriptomic analysis using Gene Set Enrichment Analysis (GSEA) and Weighted Gene Co-Expression Network Analysis (WGCNA) revealed significant differences, including a higher propensity for cellular senescence and altered metabolism in sheep samples. Further in vitro functional studies elucidated these differences, providing deeper insights into the mechanisms of IVDD.

ORGANISM(S): Ovis aries

PROVIDER: GSE302551 | GEO | 2026/01/28

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Intervertebral disc degeneration (IVDD) is a leading cause of chronic low back pain, contributing significantly to disability and imposing substantial economic burdens. Despite its prevalence, therapeutic strategies targeting IVDD remain limited. Recent advances in single-cell sequencing have highlighted the pivotal role of macrophages in driving the inflammatory microenvironment of degenerating intervertebral discs, particularly in the annulus fibrosus (AF). We demonstrate that macrophages infiltrating degenerated discs predominantly adopt the pro-inflammatory M1 phenotype, driving extracellular matrix degradation and AF degeneration.Specifically, we identify the glycoprotein SPP1 (osteopontin) as a key regulator of macrophage activation and M1 polarization within the disc, driving the expression of matrix metalloproteinases (MMPs) and exacerbating tissue damage. To modulate macrophage polarization and attenuate AF degeneration, we developed a novel targeted delivery system—@LEV@SPP1—by fusing siRNA-loaded liposomes with bacterial exosomes to achieve efficient macrophage targeting. However, the clinical translation of this system is challenged by the avascular nature and unique microenvironment of the intervertebral disc. To overcome these challenges, we developed a novel ROS-responsive, macrophage-targeted delivery system, AF-PTK@LEV@SPP1, by conjugating an AF-binding peptide (AF-P) to @LEV@SPP1 exosomes using a thioketal linker. This composite system leverages both macrophage specificity and ROS responsiveness to release the therapeutic payload upon elevated oxidative stress in the degenerate disc. In vivo experiments demonstrated that AF-PTK@LEV@SPP1 significantly reduced M1 macrophage polarization, alleviated AF degeneration, and promoted extracellular matrix repair, offering a promising strategy for long-term, targeted treatment of IVDD. These findings suggest that precisely modulating macrophage activity via AF-PTK@LEV@SPP1 holds substantial therapeutic potential for IVDD, with implications for regenerative strategies in other inflammatory disorders.

Dataset Information

Transcriptomic evaluation of ovine intervertebral disc cells as an in vitro model to explore degenerative processes

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets