Pathophysiology and current understanding of degenerative disc disease

Abstract

Degenerative disc disease is a global health concern caused by a combination of genetic, mechanical, metabolic, and environmental factors that progressively disrupt the structure and function of intervertebral discs. The underlying pathophysiology of the condition involves the breakdown of the extracellular matrix, cellular aging, oxidative stress, and persistent inflammation, all of which are driven by cytokines like interleukin 1β, tumor necrosis factor-alpha, and interleukin 6. These processes are regulated by several signaling pathways, such as nuclear factor kappa B, mitogen-activated protein kinase, and Wnt/β-catenin, which contribute to matrix degradation, dehydration, and loss of disc height. Epidemiological studies show that factors like obesity, smoking, and diabetes can accelerate the progression of the disease. While current treatments, both conservative and surgical, mainly focus on symptom relief, they do not halt or reverse the degeneration process. On the other hand, recent advancements in molecular biology and regenerative medicine offer promising new treatment options. Strategies like mesenchymal stem cell therapy, biomaterial scaffolds, and gene therapies aim to restore disc homeostasis by encouraging matrix repair and reducing harmful breakdown processes. Despite encouraging preclinical results, clinical application remains limited by challenges related to cell survival, delivery techniques, and long-term outcomes. Integrating molecular, biomechanical, and regenerative approaches could lead to more effective treatments, including potential disc regeneration.

Keywords: Intervertebral disc; Degenerative disc disease; Degeneration; Cytokines; Cellular senescence; Treatment

Core Tip: Degenerative disc disease is a multifactorial condition caused by genetic, mechanical, metabolic, and environmental factors that disrupt disc homeostasis, resulting in chronic back pain and disability. Key pathological mechanisms include extracellular matrix degradation, oxidative stress, cellular senescence, and inflammation mediated by cytokines such as interleukin 1β, tumor necrosis factor-alpha, and interleukin 6 via several signaling pathways. While current treatments primarily address symptoms, emerging regenerative approaches, including mesenchymal stem cell therapy, biomaterial scaffolds, and gene-based interventions, aim to restore disc structure and function. Integrating molecular, biomechanical, and regenerative insights offers promise for achieving true biological disc repair.