TRIM29 alleviates intervertebral disc degeneration through the PI3K/AKT/mTOR pathway

Area of Science:

• Biomedical research
• Genetics
• Molecular biology

Background:

• Intervertebral disc degeneration (IDD) is a common cause of low back pain with significant genetic underpinnings.
• Understanding the molecular mechanisms of IDD is crucial for developing effective treatments.

Purpose of the Study:

• To identify key genes and pathways involved in intervertebral disc degeneration (IDD).
• To investigate the role of tripartite motif containing 29 (TRIM29) in regulating nucleus pulposus cell (NPC) function and IDD pathogenesis.

Main Methods:

• Hierarchical dynamic weighted gene co-expression network analysis (hdWGCNA) to identify gene modules in adhesive NPCs (Adh-NPCs).
• Least absolute shrinkage and selection operator (LASSO) regression, machine learning, and receiver operating characteristic (ROC) curve analysis to pinpoint key genes.
• RNA sequencing, polymerase chain reaction (PCR), western blot, and immunohistochemistry for validation in clinical and animal models.

Main Results:

• Six key genes were identified, with tripartite motif containing 29 (TRIM29) showing a significant correlation with IDD progression.
• TRIM29 expression was validated in clinical samples and IDD animal models.
• Functional experiments revealed TRIM29 regulates intervertebral disc homeostasis and attenuates NPC inflammatory responses via the PI3K/AKT/mTOR pathway.

Conclusions:

• TRIM29 plays a critical role in maintaining intervertebral disc homeostasis and modulating inflammatory responses in NPCs.
• The PI3K/AKT/mTOR pathway is implicated in TRIM29-mediated regulation of IDD.
• TRIM29 represents a potential therapeutic target for intervertebral disc degeneration prevention and treatment.