Lactylome-based investigation of osteoarthritic subchondral bone reveals cell-specific differential expression of histone H4K12 lactylation: an experimental study

This study delineates a lactate-epigenetic axis in which osteoclast-derived lactate, transported via MCT1/MCT4, enters osteoblasts and activates osteogenic transcriptional programs through H4K12la, driving osteogenic activation and subchondral sclerosis. These findings provide novel insights into the molecular basis of subchondral bone remodeling in OA and suggest potential therapeutic targets involving lactate metabolism, lactate transport, and H4K12la-mediated epigenetic regulation to modulate OA-related subchondral bone remodeling.