Open AccessTopographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation
Author(s) -
Zheng Guoying,
Guan Binbin,
Hu Penghui,
Qi Xingying,
Wang Pingting,
Kong Yu,
Liu Zihao,
Gao Ping,
Li Rui,
Zhang Xu,
Wu Xudong,
Sui Lei
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12460
Subject(s) - direct metal laser sintering , mesenchymal stem cell , runx2 , microbiology and biotechnology , cellular differentiation , chemistry , gene expression , materials science , biology , gene , biochemistry , microstructure , crystallography
Abstract Objectives To investigate the role of hierarchical micro/nanoscale topography of direct metal laser sintering ( DMLS ) titanium surfaces in osteogenic differentiation of bone marrow mesenchymal stem cells ( BMSC s), as well as the possible underlying epigenetic mechanism. Materials and methods Three groups of titanium specimens were prepared, including DMLS group, sandblasted, large‐grit, acid‐etched ( SLA ) group and smooth titanium (Ti) group. BMSC s were cultured on discs followed by surface characterization. Cell adhesion and proliferation were examined by SEM and CCK ‐8 assay, while osteogenic‐related gene expression was detected by real‐time RT ‐ PCR . Immunofluorescence, western blotting and in vivo study were also performed to evaluate the potential for osteogenic induction of materials. In addition, to investigate the underlying epigenetic mechanisms, immunofluorescence and western blotting were performed to evaluate the global level of H3K4me3 during osteogenesis. The H3K4me3 and H3K27me3 levels at the promoter area of the osteogenic gene Runx2 were detected by Ch IP assay. Results The DMLS surface exhibits greater protein adsorption ability and shows better cell adhesion performance than SLA and Ti surfaces. Moreover, both in vitro and in vivo studies demonstrated that the DMLS surface is more favourable for the osteogenic differentiation of BMSC s than SLA and Ti surfaces. Accordingly, osteogenesis‐associated gene expression in BMSC s is efficiently induced by a rapid H3K27 demethylation and increase in H3K4me3 levels at gene promoters upon osteogenic differentiation on DMLS titanium surface. Conclusions Topographical cues of DMLS surfaces have greater potential for the induction of osteogenic differentiation of BMSC s than SLA and Ti surfaces both in vitro and in vivo . A potential epigenetic mechanism is that the appropriate topography allows rapid H3K27 demethylation and an increased H3K4me3 level at the promoter region of osteogenesis‐associated genes during the osteogenic differentiation of BMSC s.