Proposed mechanism for hMSCs osteogenesis induction on silica surfaces. The binding of integrin αVβ3 to the silica surface promotes its activation, that triggers an activation cascade that involves the three MAPK pathways, ERK, p38, but mainly JNK (reflected as wider arrow), which promotes AP-1 activation and translocation to the nucleus to activate Runx2 transcription factor. Runx2 is the finally responsible for the induction of bone extracellular matrix proteins and other osteoblast differentiation genes. In the presence of a neutralizing antibody against αVβ3, there is no activation and induction of MAPK cascades, thus no induction of bone extracellular matrix genes and hence, no differentiation.