Decoding intervertebral disc degeneration pathomechanics: from mechanisms to therapeutic horizons

BACKGROUND: Intervertebral disc degeneration (IVDD) is widely recognized as a key factor in various lumbar spine disorders. Biomechanical factors play a crucial role in maintaining homeostasis and influencing the degeneration process of the intervertebral disc (IVD). The nucleus pulposus (NP), located at the core of the disc, is responsible for distributing mechanical stresses from spinal movements, making it a primary site for degeneration. AIM OF REVIEW: This review designs to elucidate the key mechanisms of pathological mechanics in the nucleus pulposus and provide insights for biomechanically targeted therapies for disc disorders. KEY SCIENTIFIC CONCEPTS OF REVIEW: This comprehensive review provides insights into physiopathology of IVD and summarizes the biomechanical models developed over the past two decades. It specializes the mechanisms of signal transduction mediated by pathomechanics in regulating nucleus pulposus cell (NPC) homeostasis, senescence, autophagy, death, and extracellular matrix remodeling. Potential therapeutic strategies grounded in biomechanics are proposed, such as the implementation of mechanical rhythms, development of pharmacological agents targeting mechanotransduction, and hydrogel encapsulation of NPCs with adjustable mechanical properties.