The clinical success of orthopedic implants is closely
related
to their integration in the bone tissue promoted by rough device surfaces.
The biological response of precursor cells to their artificial microenvironments
plays a critical role in this process. In this study, we elucidated
the relation between cell instructivity and surface microstructure
of polycarbonate (PC)-based model substrates. The rough surface structure
(hPC) with an average peak spacing (Sm) similar to the trabecular
spacing of trabecular bone improved osteogenic differentiation of
human bone marrow mesenchymal stem cells (hBMSCs), as compared to
the smooth surface (sPC) and the surface with a moderate Sm value
(mPC). The hPC substrate promoted the cell adhesion and assembling
of F-actin and enhanced cell contractile force by upregulating phosphorylated
myosin light chain (pMLC) expression. The increased cell contractile
force led to YAP nuclear translocation and the elongation of cell
nuclei, presenting higher levels of active form of Lamin A/C. The
nuclear deformation alternated the histone modification profile, particularly
the decrease of H3K27me3 and increase of H3K9ac on the promoter region
of osteogenesis related genes (ALPL,RUNX2, andOCN). Mechanism study using inhibitors and
siRNAs elucidated the role of YAP, integrin, F-actin, myosin, and
nuclear membrane proteins in such a regulatory process of surface
topography on stem cell fate. These mechanistical insights on the
epigenetic level give a new perspective in understanding of the interaction
of substrate and stem cells as well as provide valuable criteria for
designing bioinstructive orthopedic implants.