Topographical cues of direct metal laser sintering titanium surfaces facilitate osteogenic differentiation of bone marrow mesenchymal stem cells through epigenetic regulation

• Published in: Cell proliferation Vol. 51; no. 4; pp. e12460 - n/a
• Main Authors: Zheng, Guoying, Guan, Binbin, Hu, Penghui, Qi, Xingying, Wang, Pingting, Kong, Yu, Liu, Zihao, Gao, Ping, Li, Rui, Zhang, Xu, Wu, Xudong, Sui, Lei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.08.2018; John Wiley and Sons Inc
• Subjects: Adhesion; Alkaline Phosphatase - metabolism; Biocompatibility; Biomedical materials; Bone marrow; Bone Marrow Cells - cytology; Cbfa-1 protein; Cell adhesion; Cell Adhesion - drug effects; Cell Differentiation - drug effects; Cell Proliferation - drug effects; Cell surface; Cells, Cultured; Cholecystokinin; Core Binding Factor Alpha 1 Subunit - genetics; Core Binding Factor Alpha 1 Subunit - metabolism; Demethylation; Differentiation (biology); Epigenesis, Genetic; Epigenetics; Gene expression; Grit; Humans; Immunofluorescence; In vivo methods and tests; Laser sintering; Mesenchymal stem cells; Mesenchymal Stem Cells - cytology; Mesenchymal Stem Cells - metabolism; Mesenchyme; Metals; Microscopy, Confocal; Original; Osteogenesis; Osteogenesis - drug effects; Promoter Regions, Genetic; Protein adsorption; Proteins; Stem cells; Surface Properties; Titanium; Titanium - chemistry; Titanium - pharmacology; Topography; Western blotting
• ISSN: 0960-7722; 1365-2184
• DOI: 10.1111/cpr.12460

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 (BMSCs), 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. BMSCs 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 ChIP 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 BMSCs than SLA and Ti surfaces. Accordingly, osteogenesis‐associated gene expression in BMSCs 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 BMSCs 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 BMSCs.