Stimulation of bone formation by monocyte-activator functionalized graphene oxide in vivo.
Fiche publication
Date publication
novembre 2019
Journal
Nanoscale
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BIANCO Alberto
Tous les auteurs :
Bordoni V, Reina G, Orecchioni M, Furesi G, Thiele S, Gardin C, Zavan B, Cuniberti G, Bianco A, Rauner M, Delogu LG
Lien Pubmed
Résumé
Nanosystems are able to enhance bone regeneration, a complex process requiring the mutual interplay between immune and skeletal cells. Activated monocytes can communicate pro-osteogenic signals to mesenchymal stem cells and promote osteogenesis. Thus, the activation of monocytes is a promising strategy to improve bone regeneration. Nanomaterials specifically selected to provoke immune-mediated bone formation are still missing. As a proof of concept, we apply here the intrinsic immune-characteristics of graphene oxide (GO) with the well-recognized osteoinductive capacity of calcium phosphate (CaP) in a biocompatible nanomaterial called maGO-CaP (monocytes activator GO complexed with CaP). In the presence of monocytes, the alkaline phosphatase activity and the expression of osteogenic markers increased. Studying the mechanisms of action, we detected an up-regulation of Wnt and BMP signaling, two key osteogenic pathways. The role of the immune activation was evidenced by the over-production of oncostatin M, a pro-osteogenic factor produced by monocytes. Finally, we tested the pro-osteogenic effects of maGO-CaP in vivo. maGO-CaP injected into the tibia of mice enhanced local bone mass and the bone formation rate. Our study suggests that maGO-CaP can activate monocytes to enhance osteogenesis ex vivo and in vivo.
Mots clés
Animals, Biocompatible Materials, chemistry, Bone Morphogenetic Protein 2, metabolism, Calcium Phosphates, chemistry, Cell Differentiation, drug effects, Cell Survival, drug effects, Coculture Techniques, Graphite, chemistry, Humans, Male, Mesenchymal Stem Cells, cytology, Mice, Mice, Inbred C57BL, Monocytes, cytology, Oncostatin M, metabolism, Osteoblasts, cytology, Osteogenesis, drug effects, Signal Transduction, drug effects, Tibia, drug effects, Wnt Proteins, metabolism
Référence
Nanoscale. 2019 Nov 7;11(41):19408-19421