Identification of long non-coding RNAs expressed during the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells obtained from patients with ONFH

摘要

Long non-coding RNAs (lncRNAs) are crucial for the occurrence and development of numerous diseases. Although lncRNAs are involved in the biological activities of stem cells and play crucial roles in stem cell differentiation, the expression of specific lncRNAs during human bone marrow-derived mesenchymal stem cell (hBMSC) osteogenic differentiation in osteonecrosis of the femoral head (ONFH) and their regulatory roles have not yet been fully elucidated. To the best of our knowledge, the present study is the first to characterize lncRNA expression profiles during hBMSC osteogenic differentiation in ONFH using microarray analysis and RT-qPCR to confirm the microarray data. A total of 24 downregulated and 24 upregulated lncRNAs were identified and the results of RT-qPCR were found to be consistent with those of microarray analysis. Bioinformatics analyses, using the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, were conducted to explore the possible mechanisms and identify the signaling pathways that the lncRNAs are involved in. GO analysis revealed significant changes in the intracellular organelle, Ras protein signal transduction and transferase activity. KEGG pathway analysis revealed that the lncRNAs were closely associated with fatty acid metabolism, apoptosis and the TGF-ss signaling pathway. The overexpression of MAPT antisense RNA 1 (MAPT-AS1) was found to promote osteogenesis and inhibit the adipogenesis of hBMSCs at the cellular and mRNA levels. On the whole, the findings of the present study identified the lncRNAs and their roles in hBMSCs undergoing osteogenic differentiation in ONFH and provide a new perspective for the pathogenesis of ONFH.