Multi-omics and causal inference reveal lactylation-based osteoblast regulatory networks and drug candidates - PubMed
4 hours ago
- #Drug repurposing
- #Osteoblast regulation
- #Multi-omics
- Bone loss-related disorders are a growing global health challenge due to impaired osteoblast activity.
- Lactate-derived lysine lactylation, a glycolysis-linked PTM, may regulate osteoblast differentiation and bone homeostasis.
- Multi-omics profiling, Mendelian randomization (MR), and computational modeling were used to study lactylation-mediated osteogenic regulation.
- Dynamic proteomic and lactylome changes during osteoblast differentiation identified 43 key proteins with altered expression and lactylation.
- MR analysis identified NANS and SPTLC1 as causal regulators of bone mineral density.
- Molecular dynamics simulations showed lactylation-driven functional remodeling of NANS and SPTLC1.
- Network pharmacology suggested FDA-approved compounds like Suramin sodium and Paritaprevir as potential osteogenic agents.
- The study provides a framework for discovering small molecules that mimic lactylation-induced conformational changes for drug repurposing.