LncRNAs Transcriptome Analysis Revealed HIF1A-AS1 as a Mediator of Bone Remodeling Associated with the Micro Structured Titanium Surface

Abstract

Because of their hierarchical structure, sandblasted and acid etched (SLA) titanium implants are widely used to promote bone apposition. Understanding the molecular mechanisms of SLA titanium implant-enhanced osteogenesis provides clues to improve surface modification methods. However, the epigenetics mechanisms involving SLA surface weren't clear. In this study, we systematically identify the long noncoding RNAs (lncRNAs) and mRNAs related to the superior osseointegration induced by SLA. The mechanical, chemical, and osteogenic characteristics of the fabricated SLA and smooth polished (SMO) titanium surfaces were compared and analyzed. Thousands of lncRNAs and mRNAs within osteogenesis-associated biological processes were differentially expressed in human bone marrow-derived mesenchymal stem cells (hBMSCs) on SLA surface compared with SMO surface. We constructed an mRNA-lncRNA co-expression network to gain insight into the role of differentially expressed lncRNAs and validated the co-expression of HIF1A-AS1/VEGFA, IGF2-AS/GLI2, and HOXD-AS1/FGF10. Further, we identified that the knockdown of HIF1A-AS1 not only decreased the expression of VEGFA, but also significantly inhibited the osteogenic differentiation of hBMSCs. Meanwhile, we found that silencing of lncRNA HIF1A-AS1 reduced the level of phosphorylated mitogen-activated protein kinase (p-MAPK). In conclusion, our study indicated that the SLA surface enhanced osteogenesis partly through differential regulation of lncRNAs, like HIF1A-AS1. Our study also increased the understanding of the role lncRNA HIF1A-AS1 in the differentiation of osteoblast, providing clues for the potential optimization of titanium implant surface.