Research Progress on the Mechanisms and Therapeutic Prospects of Metabolic Reprogramming and Lactylation in Intervertebral Disc Degeneration
GUO Jie1, HUANG Tao1, ZHANG Yanjun2*
IVDD (intervertebral disc degeneration) is the primary pathological basis of chronic low back pain, and its progression is closely associated with inflammatory responses, extracellular matrix degradation, and various forms of cell death. Recent studies have demonstrated that significant metabolic reprogramming occurs during IVDD, in which nucleus pulposus cells shift from oxidative phosphorylation to glycolysis, leading to lactate accumulation and formation of an acidic microenvironment. Lactate not only acts as a metabolic byproduct but also regulates inflammatory responses, immune cell polarization, and programmed cell death through protein lactylation. Lactylation has been shown to influence key processes, including the NF-κB signaling pathway, NLRP3 inflammasome activation, and ferroptosis, thereby promoting the progression of IVDD. Meanwhile, therapeutic strategies targeting metabolic reprogramming and lactylation have demonstrated potential in delaying IVDD progression. This review systematically summarizes the roles of metabolic reprogramming and lactylation in IVDD and discusses their potential therapeutic implications, aiming to provide a theoretical basis for precision treatment of IVDD.
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