Lactate Metabolism in the Intervertebral Disc: Mechanistic Insights and Pathological Implications.

The intervertebral disc (IVD) is the largest avascular structure in the human body, and its nucleus pulposus (NP) cells predominantly generate large amounts of lactate through glycolysis, accompanied by an acidic microenvironment-features that represent characteristic metabolic traits of disc cells. In recent years, knowledge of the biological roles of lactate has undergone a conceptual shift. On the one hand, lactate can serve as a context-dependent auxiliary biofuel in specific regions of the IVD, particularly within annulus fibrosus (AF) regions adjacent to the NP. On the other hand, lactate functions in disc cells as a signaling molecule and a metabolic-epigenetic regulator, influencing transcriptional programs through lactylation and modulating multiple molecular pathways associated with cellular stress adaptation and fate determination. This review summarizes current knowledge on lactate production, transport, and clearance in the intervertebral disc, as well as emerging evidence for the roles of lactate in disc health and pathophysiology. In addition, we outline research perspectives and future directions aimed at advancing our understanding of lactate biology and evaluating its potential as a therapeutic target for intervertebral disc degeneration.