mTORC2 regulates hierarchical micro/nano topography‐induced osteogenic differentiation via promoting cell adhesion and cytoskeletal polymerization

• Published in: Journal of cellular and molecular medicine Vol. 25; no. 14; pp. 6695 - 6708
• Main Authors: Gao, Qian, Hou, Yuying, Li, Zhe, Hu, Jinyang, Huo, Dawei, Zheng, Huimin, Zhang, Junjiang, Yao, Xiaoyu, Gao, Rui, Wu, Xudong, Sui, Lei
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.07.2021; John Wiley and Sons Inc
• Subjects: Animals; Cbfa-1 protein; cell adhesion; Cell adhesion & migration; Cell Adhesion - genetics; Cell adhesion molecules; Cell differentiation; Cell Differentiation - genetics; Cell Proliferation - drug effects; Cells, Cultured; Core Binding Factor Alpha 1 Subunit - genetics; Cytoskeleton; Cytoskeleton - genetics; Gene expression; Heat treatments; hierarchical micro/nano structure; Humans; Kinases; Lasers; Mechanistic Target of Rapamycin Complex 2 - genetics; Mesenchymal Stem Cells - drug effects; Mice; mTORC2; Original; Osteocalcin - genetics; Osteogenesis; Osteogenesis - genetics; osteogenic differentiation; Penicillin; Polymerization; Polymerization - drug effects; Proteins; Signal transduction; Signal Transduction - drug effects; Surface Properties - drug effects; Titanium; Titanium - pharmacology; Topography; Transplants & implants; hierarchical micro/nano structure; mTORC2; cytoskeleton; cell adhesion; osteogenic differentiation
• ISSN: 1582-1838; 1582-4934
• DOI: 10.1111/jcmm.16672

Surface topography acts as an irreplaceable role in the long‐term success of intraosseous implants. In this study, we prepared the hierarchical micro/nano topography using selective laser melting combined with alkali heat treatment (SLM‐AHT) and explored the underlying mechanism of SLM‐AHT surface‐elicited osteogenesis. Our results show that cells cultured on SLM‐AHT surface possess the largest number of mature FAs and exhibit a cytoskeleton reorganization compared with control groups. SLM‐AHT surface could also significantly upregulate the expression of the cell adhesion‐related molecule p‐FAK, the osteogenic differentiation‐related molecules RUNX2 and OCN as well as the mTORC2 signalling pathway key molecule Rictor. Notably, after the knocked‐down of Rictor, there were no longer significant differences in the gene expression levels of the cell adhesion‐related molecules and osteogenic differentiation‐related molecules among the three titanium surfaces, and the cells on SLM‐AHT surface failed to trigger cytoskeleton reorganization. In conclusion, the results suggest that mTORC2 can regulate the hierarchical micro/nano topography‐mediated osteogenesis via cell adhesion and cytoskeletal reorganization.