Apoptotic Pathway in Intervertebral Disc Degeneration: From Molecular Pathways to Clinical Interventions

Area of Science:

• Biomedical Science
• Cell Biology
• Regenerative Medicine

Background:

• Apoptosis is a key driver of intervertebral disc degeneration (IVDD), a major cause of chronic low back pain.
• IVDD affects nucleus pulposus, annulus fibrosus, and cartilage endplate cells, impacting disc function.

Purpose of the Study:

• To review the cellular and molecular mechanisms of disc cell apoptosis in IVDD.
• To explore the role of oxidative stress, inflammation, mechanical load, and metabolic disturbances in apoptosis.
• To examine current and emerging therapeutic strategies for IVDD.

Main Methods:

• Comprehensive literature search (2000-2025) for narrative review.
• Synthesis of current knowledge on apoptosis pathways in IVDD.
• Analysis of therapeutic interventions and their translational potential.

Main Results:

• Apoptosis is triggered by intrinsic, extrinsic, ER stress, and autophagy-related pathways.
• Diabetes, inflammation, oxidative stress, and mechanical factors exacerbate disc cell apoptosis.
• Therapies including antioxidants, anti-inflammatories, autophagy modulators, stem cells, and gene therapy show preclinical promise.

Conclusions:

• Understanding apoptosis mechanisms is crucial for developing mechanism-based IVDD therapies.
• Future treatments should focus on cellular preservation and matrix integrity for IVDD.
• A paradigm shift towards addressing the root cause of IVDD is needed for effective treatment.