Abstract
Lactoferrin (LF) has demonstrated stimulation of osteogenic differentiation of mesenchymal stem cells (MSCs). Long non-coding RNAs (lncRNAs) participate in regulating the osteogenic differentiation processes. However, the impact of LF on lncRNA expression in MSC osteogenic differentiation is poorly understood. Our aim was to investigate the effects of LF on lncRNAs expression profiles, during osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs), by RNA sequencing. A total number of 1331 putative lncRNAs were identified in rBMSCs during osteogenic differentiation in the study. LF influenced the expression of 120 lncRNAs (differentially expressed lncRNAs [DELs], Fold change > 1.5 or < −1.5; p < 0.05) in rBMSCs on day 14 of osteogenic differentiation, consisted of 60 upregulated and 60 down-regulated. Furthermore, the potential functions of DELs were of prediction by searching their target cis- and trans-regulated protein-coding genes. The bioinformatic analysis of DELs target gene revealed that LF led to the disfunction of transforming growth factor beta stimulus (TGF-β) and positive regulation of I-κappa B kinase/NF-κappa B signaling pathway, which may relate to osteogenic differentiation of rBMSCs. Our work is the first profiling of lncRNA in osteogenic differentiation of rBMSCs induced by LF, and provides valuable insights into the potential mechanisms for LF promoting osteogenic activity.
Highlights
Bone marrow mesenchymal stem cells (BMSCs) are known to be an essential sources of progenitor cells, with multipotent and self-renewal capacity to differentiate into various cell types, including chondrocytes, osteoblasts, and adipocytes [1,2]
The results show that the mechanism for enhancement of the osteogenic differentiation of rat bone marrow mesenchymal stem cells (rBMSCs) by LF-treatment might be attributed to regulation of Long non-coding RNAs (lncRNAs) expression
The results show that lactoferrin affected the lncRNAs expression during osteogenic differentiation in rBMSCs, the mechanism of osteotropic activity of LF referred to the lncRNA regulation
Summary
Bone marrow mesenchymal stem cells (BMSCs) are known to be an essential sources of progenitor cells, with multipotent and self-renewal capacity to differentiate into various cell types, including chondrocytes, osteoblasts, and adipocytes [1,2]. The osteogenic differentiation of BMSCs is responsible for bone formation, regeneration, and repair [3]. Some naturally existing nutrients and bioactive compounds, including fatty acid [4], carotenoids [5,6], flavonoids [7,8] phenolic acids [9], and peptides [10,11] have shown that enhanced osteogenic differentiation of osteoblasts and mesenchymal stem cells (MSCs) have attracted more attention as a source of clinical and functional food applications for improving bone health. The mechanisms of LF-promoting osteogenic activity were unclear
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