Tumor necrosis factor-α: a key contributor to intervertebral disc degeneration

Intervertebral disc (IVD) degeneration (IDD) is the most common cause leading to low back pain (LBP), which is a highly prevalent, costly, and crippling condition worldwide. Current treatments for IDD are limited to treat the symptoms and do not target the pathophysiology. Tumor necrosis factor-alpha (TNF-alpha) is one of the most potent pro-inflammatory cytokines and signals through its receptors TNFR1 and TNFR2. TNF-alpha is highly expressed in degenerative IVD tissues, and it is deeply involved in multiple pathological processes of disc degeneration, including matrix destruction, inflammatory responses, apoptosis, autophagy, and cell proliferation. Importantly, anti-TNF-alpha therapy has shown promise for mitigating disc degeneration and relieving LBP. In this review, following a brief description of TNF-alpha signal transduction, we mainly focus on the expression pattern and roles of TNF-alpha in IDD, and summarize the emerging progress regarding its inhibition as a promising biological therapeutic approach to disc degeneration and associated LBP. A better understanding will help to develop novel TNF-alpha-centered therapeutic interventions for degenerative disc disease.