Lactate and lactylation in intervertebral disc degeneration

Area of Science:

• Biochemistry
• Cell Biology
• Biomedical Engineering

Background:

• The intervertebral disc (IVD) has a hypoxic microenvironment due to avascularity, promoting anaerobic glycolysis and lactate accumulation.
• Lactate, a key metabolic byproduct, significantly influences cell differentiation and fate in physiological and pathological conditions, including degenerative diseases.

Purpose of the Study:

• To review the critical role of lactate and lactylation in intervertebral disc degeneration (IVDD).
• To explore therapeutic strategies targeting lactate metabolism for improved treatment outcomes in IVDD.

Main Methods:

• Literature review focusing on cellular metabolism, lactate signaling, and lactylation in the IVD.
• Analysis of existing evidence on the impact of lactate dehydrogenases (LDHs) and monocarboxylate transporters (MCTs) in IVDD.

Main Results:

• Lactate accumulation is a hallmark of the hypoxic IVD microenvironment and contributes to IVDD progression.
• Lactate modulates cellular signaling pathways and promotes lactylation, impacting cell fate.
• Targeting LDHs and MCTs presents a promising therapeutic avenue for IVDD.

Conclusions:

• Understanding lactate regulation and lactylation is crucial for mitigating IVDD.
• Modulating lactate metabolism offers significant therapeutic potential for treating intervertebral disc degeneration.