Long Noncoding RNA FAM83H-AS1 Modulates SpA-Inhibited Osteogenic Differentiation in Human Bone Mesenchymal Stem Cells

Abstract

Copyright © 2020 American Society for Microbiology. All Rights Reserved. Osteomyelitis, an infection of the bone and bone marrow, imposes a heavy burden on public health care systems owing to its progressive bone destruction and sequestration. Human bone mesenchymal stem cells (hBMSCs) play a key role in the process of bone formation, and mounting evidence has confirmed that long noncoding RNAs (lncRNAs) are involved in hBMSC osteogenic differentiation. Nevertheless, the exact function and molecular mechanism of lncRNAs in osteogenic differentiation during osteomyelitis development remain to be explored. In this study, hBMSCs were treated with staphylococcal protein A (SpA) during osteogenic differentiation induction to mimic osteomyelitis in vitro. The results of lncRNA microarray analysis revealed that FAM83H-AS1 presented the lowest expression among the significantly downregulated lncRNAs. Functionally, ectopic expression of FAM83H-AS1 contributed to osteogenic differentiation of SpA-induced hBMSCs. Additionally, our findings revealed that FAM83H-AS1 negatively regulated microRNA 541-3p (miR-541-3p), and WNT3A was validated as a target gene of miR-541-3p. Mechanically, FAM83H-AS1 elevated WNT3A expression by competitively binding with miR-541-3p. Lastly, it was demonstrated that FAM83H-AS1/miR-541-3p/WNT3A ameliorated SpA-mediated inhibition of the osteogenic differentiation of hBMSCs, which provided a novel therapeutic strategy for patients with osteomyelitis.