Objective To review the research progress on lactylation modification in the pathogenesis of osteoarthritis (OA). Methods Relevant studies published in recent years on lactate metabolism and lactylation modification in OA were retrieved and analyzed, summarizing the molecular mechanisms of lactylation and its regulatory roles in different cells and pathological processes. Results Lactate, as the major metabolic product of glycolysis, not only participates in energy metabolism but also plays a crucial role in OA progression through lactylation modification. Lactate-driven histone and non-histone lactylation regulate gene transcription and cellular functions, contributing to chondrocyte metabolic reprogramming, extracellular matrix (ECM) synthesis and degradation, cell proliferation and apoptosis, as well as ferroptosis. In fibroblast-like synoviocytes, lactylation modification promotes cellular senescence and the release of inflammatory factors; in immune cells, lactylation regulates inflammatory responses by influencing macrophage polarization and intercellular communication. Overall, lactylation modification exhibits a dual effect in OA: it aggravates ECM degradation and inflammation on the one hand, but under specific microenvironments, it also promotes repair and regeneration. However, the site-specificity, cell-type heterogeneity, and cross-talk of lactylation with other epigenetic modifications remain to be further clarified. Conclusion Lactylation modification provides a novel perspective for understanding the metabolic and epigenetic mechanisms of OA and may serve as a potential biomarker and therapeutic target. Future studies combining multi-omics approaches to map the global lactylation landscape, together with small-molecule inhibitors, epigenetic editing tools, and regenerative medicine strategies, may enable precise regulation of lactylation, offering new strategies to delay or even reverse OA progression.
Lactate was originally thought to be a metabolic waste product of glycolysis produced by cells in hypoxic environment. In recent years, increasing evidence has indicated that lactate plays a crucial role in the physiological and pathological processes of the retina. Lactate is transported via monocarboxylate transporters in different retinal cell types such as photoreceptor cells and Müller cells to maintain the high metabolic demand of the retina. In addition to serving as oxiditive substrate for energy, lactate can mediate intracellular signal transduction through receptor G protein-coupled receptor 81, participating in the maintenance of retinal homeostasis and the progression of pathological neovascularization. Moreover, lactate-mediated protein lactylation directly regulates gene expression in microglia and T lymphocytes, which has gradually become a new hotspot in the field of retinal pathological neovascularization and neuroinflammation. Therefore, the regulation of lactate metabolism may provide novel perspectives for the treatment of retinal lactic acid metabolism disorders such as age-related macular degeneration and retinitis pigmentosa.
