Work

Magnesium-based implants accelerate femoral fracture healing through promoting histone lactylation-mediated osteoclastogenesis inhibition

Year: 2025

Type: article

Abstract: Femoral fractures are a prevalent clinical condition, and magnesium (Mg)-based implants have shown promise as an effective treatment. However, the mechanisms by which Mg promotes fracture healing remain elusive. In this study, we demonstrated that Mg-containing intramedullary nails (Mg-IMNs) significantly enhanced femoral fracture healing in rats by inhibiting osteoclastogenesis. Mg ions (Mg2+) stimulated intracellular lactate production, which acted as a substrate for histone lactylation-a recently identified epigenetic modification. In vitro experiments showed that Mg2+ enhanced histone lactylation, thereby suppressing osteoclast maturation by downregulating the key transcription factor NFATc1. Additionally, we identified the P300/H3K18LA/HDAC1 pathway as a pivotal mediator of Mg2+-induced histone lactylation and the subsequent inhibition of osteoclastogenesis. In vivo experiments demonstrated that lactate administration replicated the effects of Mg-IMNs, while blocking lactate production reversed these effects. Together, these findings uncover a novel mechanism by which Mg2+ promotes fracture healing through histone lactylation-mediated inhibition of osteoclastogenesis, offering potential therapeutic strategies for enhancing fracture repair via this epigenetic pathway.

Source: Life Sciences

DOI: 10.1016/j.lfs.2025.123639