resumo
Bone-related disorders are a major cause of disability and escalating healthcare costs, driving interest in tissue engineering approaches with mesenchymal stem cells (MSC). To avoid the use of synthetic osteogenic compounds, this study investigates the metabolic adaptations of MSC during nanovibration (or nanokicking, NK)-induced osteodifferentiation in the absence of chemical inducers. Using both conventional gene markers and an integrated metabolomics/lipidomics strategy, we identified a slow-paced osteodifferentiation process marked by subtle, partially reversible intracellular changes, alongside more pronounced and largely irreversible extracellular modifications.During the first 7 days of stimulation, cells exhibited high energy demands and phosphocholine hydrolysis, both of which diminished thereafter. In contrast, early membrane remodeling persisted up to day 21, likely supporting increased membrane fluidity, vesicle formation, and the activation of signaling cascades. Beyond day 7, enhanced redox regulation, antioxidant activity, and glycerolipid redirection toward phospholipid biosynthesis were evident. Concurrent sphingolipid modulation may facilitate the production of bioactive lipids, phosphate release for mineralization, and lipid raft assembly. NK emerged as a more targeted strategy for osteocommitment compared to traditional protocols, with cellular metabolic adatations potentially involving the activation of several kinases, glutathione peroxidase, and lipophagy. This global metabolomics approach unveiled the key metabolic features of NK-induced osteodifferentiation of human adipose-derived MSC and underscored the potential of extracellular metabolite signatures as real-time indicators of differentiation dynamics.
autores
Bispo DSC, Tsimbouri PM, JH Haggarty, Graça I, Rodrigues JEA, Oliveira MB, Mano JF, Dalby MJ, Gil AM
nossos autores
Ana Maria Pissarra Coelho Gil
Professor Associado com Agregação
Daniela Bispo
Estudante de doutoramento
Inês C. R. Graça
Bolseiro de investigação
João A. Rodrigues
Investigador Júnior
João Mano
Professor Catedrático
Mariana Braga de Oliveira
Investigador AuxiliarProjectos
CICECO - Aveiro Institute of Materials (UIDB/50011/2020)
CICECO - Aveiro Institute of Materials (UIDP/50011/2020)
Associated Laboratory CICECO-Aveiro Institute of Materials (LA/P/0006/2020)
Metabolite-activated 3D stem cell differentiation into bone (BetterBone)
agradecimentos
This work was developed within the scope of the CICECO-Aveiro Institute of Materials, UIDB/50011/2020 project (doi: 10.54499/UIDB/50011/2020), UIDP/50011/2020 (doi: 10.54499/UIDP/ 50011/2020) and LA/P/0006/2020 (doi:10.54499/LA/P/0006/2020), financed by national funds through the FCT/MCTES (PIDDAC). We acknowledge funds from the Foundation for Science and Technology through the BetterBone project (2022.04286.PTDC, doi: 10.54499/2022.04286.PTDC), the Portuguese National NMR Network (RNRMN), supported by Infrastructure Project Nº 022161 (co-financed by FEDER through COMPETE 2020, POCI and PORL and FCT through PIDDAC); and FCT/SPQ PhD grant (DSCB) (SFRH/BD/150655/2020, doi: 10.54499/SFRH/BD/150655/2020). EPSRC grant EP/P001114/1.