Multi-omics and causal inference reveal lactylation-based osteoblast regulatory networks and drug candidates

osteoblast models, we mapped dynamic proteomic and lactylome changes during differentiation, identifying 43 key proteins with concurrent alterations in expression and lactylation. Integrated MR analysis of human genetic data identified NANS and SPTLC1 as causal regulators of bone mineral density. Molecular dynamics simulations revealed lactylation-driven functional remodeling of these proteins, and network pharmacology suggested FDA-approved compounds (e.g., Suramin sodium and Paritaprevir) as potential osteogenic agents. This study advances mechanistic understanding of osteogenesis and provides a framework for discovering small molecules that mimic lactylation-induced conformational changes for drug repurposing in clinical applications.