Lactylation driven by lactate metabolism in the disc accelerates intervertebral disc degeneration: A hypothesis

The imbalance of intracellular homeostasis is closely related to intervertebral disc degeneration (IDD). Lactate, the final product of glycolysis, is a potential biomarker of IDD. The disorder of lactate transport and metabolism can significantly increase the concentration of lactate and affect the acidity of extracellular matrix, which is the main cause of the acidic environment in the disc and IDD. The metabolic function of lactate has been studied in depth, but its non-metabolic function is still unclear. The newly discovered modification of histone lactylation provides a new idea for the mechanism of IDD. The production and accumulation of lactate results in increased modification level of histone lactylation in intervertebral disc. Furthermore, it will affect genome-level transcriptional regulation, regulate the function and fate of nucleus pulposus cells, and lead to the occurrence and development of intervertebral disc degeneration. During the process of IDD, lactate production and histone lactylation modification may be an important regulatory mechanism of IDD, which is worthy of further investigation.