RT Journal Article T1 Metabolomic characterization of MC3T3-E1pre-osteoblast differentiation induced by ipriflavone-loaded mesoporous nanospheres A1 Casarrubios Molina, Laura A1 Cicuéndez Maroto, Mónica A1 Polo Montalvo, Alberto A1 Feito Castellano, María José A1 Martínez Del Pozo, Álvaro A1 Arcos Navarrete, Daniel A1 Duarte, Iola F. A1 Portolés Pérez, María Teresa AB This study reports on the metabolic changes accompanying the differentiation of MC3T3-E1 osteoprogenitor cells induced by mesoporous bioactive glass nanospheres (nMBG) loaded with ipriflavone (nMBG-IP). Ipriflavone (IP) is a synthetic isoflavone known for inhibiting bone resorption, maintaining bone density, and preventing osteoporosis. Delivering IP intracellularly is a promising strategy to modulate bone remodeling at significantly lower doses compared to free drug administration. Our results demonstrate that nMBG are efficiently internalized by pre-osteoblasts and, when loaded with IP, induce their differentiation. This differentiation process is accompanied by pronounced metabolic alterations, as monitored by NMR analysis of medium supernatants and cell extracts (exo- and endo-metabolomics, respectively). The main effects include an early-stage intensification of glycolysis and changes in several metabolic pathways, such as nucleobase metabolism, osmoregulatory and antioxidant pathways, and lipid metabolism. Notably, the metabolic impacts of nMBG-IP and free IP were very similar, whereas nMBG alone induced only mild changes in the intracellular metabolic profile without affecting the cells’ consumption/secretion patterns or lipid composition. This finding indicates that the observed effects are primarily related to IP-induced differentiation and that nMBG nanospheres serve as convenient carriers with both efficient internalization and minimal metabolic impact. Furthermore, the observed link between pre-osteoblast differentiation and metabolism underscores the potential of utilizing metabolites and metabolic reprogramming as strategies to modulate the osteogenic process, for instance, in the context of osteoporosis and other bone diseases. PB Elsevier SN 2772-9508 YR 2024 FD 2024 LK https://hdl.handle.net/20.500.14352/109869 UL https://hdl.handle.net/20.500.14352/109869 LA eng NO Laura Casarrubios, Mónica Cicuéndez, Alberto Polo-Montalvo, María José Feito, Álvaro Martínez-del-Pozo, Daniel Arcos, Iola F. Duarte, María Teresa Portolés, Metabolomic characterization of MC3T3-E1pre-osteoblast differentiation induced by ipriflavone-loaded mesoporous nanospheres, Biomaterials Advances, Volume 166, 2025, 214085, https://doi.org/10.1016/j.bioadv.2024.214085. NO Ministerio de Ciencia, Innovación y Universidades (España) DS Docta Complutense RD 24 abr 2025