AutoriF. Viti, M. Landini, A. Mezzelani, L. Petecchia, L. Milanesi, S. Scaglione
AbstractThe culture of progenitor mesenchymal stem cells (MSC) onto osteoconductive materials to
induce a proper osteogenic differentiation and mineralized matrix regeneration represents a
promising and widely diffused experimental approach for tissue-engineering (TE) applications
in orthopaedics. Among modern biomaterials, calcium phosphates represent the best
bone substitutes, due to their chemical features emulating the mineral phase of bone tissue.
Although many studies on stem cells differentiation mechanisms have been performed
involving calcium-based scaffolds, results often focus on highlighting production of in vitro
bone matrix markers and in vivo tissue ingrowth, while information related to the biomolecular
mechanisms involved in the early cellular calcium-mediated differentiation is not well elucidated
yet. Genetic programs for osteogenesis have been just partially deciphered, and
the description of the different molecules and pathways operative in these differentiations is
far from complete, as well as the activity of calcium in this process. The present work aims
to shed light on the involvement of extracellular calcium in MSC differentiation: a better
understanding of the early stage osteogenic differentiation program of MSC seeded on calcium-
based biomaterials is required in order to develop optimal strategies to promote osteogenesis
through the use of new generation osteoconductive scaffolds. A wide spectrum of
analysis has been performed on time-dependent series: gene expression profiles are
obtained from samples (MSC seeded on calcium-based scaffolds), together with related
microRNAs expression and in vivo functional validation. On this basis, and relying on literature
knowledge, hypotheses are made on the biomolecular players activated by the biomaterial
calcium-phosphate component. Interestingly, a key role of miR-138 was highlighted,
whose inhibition markedly increases osteogenic differentiation in vitro and enhance ectopic
bone formation in vivo. Moreover, there is evidence that Ca-P substrate triggers osteogenic
differentiation through genes (SMAD and RAS family) that are typically regulated during
dexamethasone (DEX) induced differentiation.
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Autori IBFLoredana PETECCHIA, Federica VITI
Linee di Ricerca IBFMD.P01.001.001