The role of bioactive nanofibers in enamel regeneration mediated through integrin signals acting upon C/EBPα and c-Jun

摘要: Enamel formation involves highly orchestrated intracellular and extracellular events; following development, the tissue is unable to regenerate, making it a challenging target for engineering. We previously demonstrated ability trigger enamel differentiation regeneration in embryonic mouse incisor using self-assembling matrix that displayed integrin-binding epitope RGDS (Arg-Gly-Asp-Ser). To further elucidate signaling pathways responsible this phenomenon, we explore here coupling response of integrin receptors biomaterial subsequent downstream gene expression profiles. demonstrate artificial activates focal adhesion kinase (FAK) increase phosphorylation both c-Jun N-terminal (JNK) its transcription factor (c-Jun). Inhibition FAK blocked activation identified matrix-mediated pathways, while independent inhibition JNK nearly abolished phosphorylated-c-Jun (p-c-Jun) attenuated promote regeneration. Cognate binding sites amelogenin promoter were be transcriptionally up-regulated p-c-Jun. Furthermore, induced as evidenced by an increased abundance amelogenin, main protein expressed during formation, CCAAT enhancer alpha (C/EBPα), which known activator expression. Elucidating these cues not only provides guidelines design synthetic regenerative strategies opportunities manipulate regulate regeneration, but can provide insight into molecular mechanisms involved formation.