Abstract
Bone defects caused heavy social and economic burdens worldwide. Nel‐like molecule, type 1 (NELL‐1) could enhance the osteogenesis and the repairment of bone defects, while the specific mechanism remains to be elucidated. Circular RNAs (circRNAs) have been found to play critical roles in the tissue development and serve as biomarkers for various diseases. However, it remains unclear that the expression patterns of circRNAs and the roles of them played in recombinant NELL‐1‐induced osteogenesis of human adipose‐derived stem cells (hASCs). In this study, we performed RNA‐sequencing to investigate the expression profiles of circRNAs in recombinant NELL‐1‐induced osteogenic differentiation and identified two key circRNAs, namely circRFWD2 and circINO80. These two circRNAs were confirmed to be up‐regulated during recombinant NELL‐1‐induced osteogenesis, and knockdown of them affected the positive effect of NELL‐1 on osteogenesis. CircRFWD2 and circINO80 could interact with hsa‐miR‐6817‐5p, which could inhibit the osteogenesis. Silencing hsa‐miR‐6817‐5p could partially reverse the negative effect of si‐circRFWD2 and si‐circINO80 on the osteogenesis. Therefore, circRFWD2 and circINO80 could regulate the expression of hsa‐miR‐6817‐5p and influence the recombinant NELL‐1‐induced osteogenic differentiation of hASCs. It opens a new window to better understanding the effects of NELL‐1 on the osteogenic differentiation of hASCs and provides potential molecular targets and novel methods for bone regeneration efficiently and safely.
Highlights
Bone defects, which caused by congenital diseases, trauma and surgeries, have led to enormous burdens and affect the people's quality of life seriously, but the treatment of critical bone defects remains a difficult biomedical problem.[1]
It remains unclear that the comprehensive expression patterns of circRNAs and the roles of them played in the NELL‐1‐induced osteogenesis of Human adipose‐derived stem cells (hASCs)
Our results indicated that circRFWD2 and circINO80 could regulate the expression of hsa‐miR‐6817‐5p and influence the recombinant NELL‐1‐induced osteogenesis of hASCs
Summary
Bone defects, which caused by congenital diseases, trauma and surgeries, have led to enormous burdens and affect the people's quality of life seriously, but the treatment of critical bone defects remains a difficult biomedical problem.[1]. Unlike linear RNAs, they hold a covalently closed loop, keeping them stable and resistant to RNase R digestion.[18,19] High throughput sequencing has demonstrated that circRNAs were widely and abundantly distributed in the eukaryotic transcriptome with tis‐ sue‐specific expression.[20] Functionally, circRNAs could regulate the protein function via cap‐independent mechanism, affect the splicing of parental genes and serve as the microRNAs (miRNAs) sponges to cross‐talk with miRNAs.[21,22,23] Emerging evidence has proven that cir‐ cRNAs played important roles in the development of normal tissues and various diseases, such as cardiovascular diseases, age‐related diseases, autoimmune diseases and tumours.[24,25,26,27,28,29,30] Their functions as potential biomarkers were gradually discovered in cancers and neu‐ rodegenerative disorders.[31,32] it remains unclear that the comprehensive expression patterns of circRNAs and the roles of them played in the NELL‐1‐induced osteogenesis of hASCs. In present study, we performed RNA‐sequencing and compared the expression profiles of circRNAs between recombinant NELL‐1‐induced osteogenic differentiation group (NG) and general osteogenic differen‐ tiation group (OG). Our results indicated that circRFWD2 and circINO80 could regulate the expression of hsa‐miR‐6817‐5p and influence the recombinant NELL‐1‐induced osteogenesis of hASCs
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