Abstract

Pain, physical dysfunction, and mental disorders caused by bone nonunion bring great burden to patients. Bone mesenchymal stem cells (BMSCs) isolated from bone nonunion patients with poor proliferation and osteogenic ability are compared with that from normal bone-healing patients. Long noncoding RNAs (lncRNAs) are a class of RNAs that are more than 200 nucleotides in length, lack an open-reading frame encoding a protein, and have little or no protein-coding function, and could regulate gene expression, which is involved in the regulation of important life activities, such as growth, development, aging, and death at epigenetic, transcriptional, and post-transcriptional levels. In this study, we intended to investigate the difference of lncRNA expression between patients with nonunion and normal fracture healing. Our result found that lncRNA ENST00000563492 was downregulated in bone nonunion tissues. LncRNA ENST00000563492 promotes osteogenic differentiation of BMSCs through upregulating the expression of CDH11. On the other hand, LncRNA ENST0000563492 could improve the osteogenesis–angiogenesis coupling process through enhancing the expression of VEGF during osteogenic differentiation of BMSCs. LncRNA ENST00000563492 functions as a ceRNA for miR-205-5p that was targeting CDH11 and VEGF. LncRNA ENST00000563492 could promote the osteogenesis of BMSCs in vivo. Our result indicated that lncRNA ENST00000563492 may be a new target for bone nonunion.

Highlights

  • Most fractures heal after surgery, 5–10% of patients still develop nonunion after treatment

  • The results of sequencing analysis were verified by qRT-PCR and showed that the expression of Long noncoding RNAs (lncRNAs) ENST00000563492 was significantly increased in normal fractured tissue compared with that in nonunion tissue (Fig. 1c)

  • The results showed that lncRNA ENST00000563492 expression increased most significantly during osteogenic differentiation of Bone mesenchymal stem cells (BMSCs) (Fig. 1d)

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Summary

Introduction

Most fractures heal after surgery, 5–10% of patients still develop nonunion after treatment. Limb dysfunction, and psychological disorders caused by nonunion cause great pain to patients and families, increasing the financial burden on families and society[1]. The traditional treatment method included that remove the hardened bone, clean the non-connected end tissue, cut the. To explore the mechanisms of nonunion and healing, many scholars have conducted related research in cell biology and molecular biology. Boyan et al.[2] first studied the cells isolated from the scar tissue of the nonunion, Official journal of the Cell Death Differentiation Association. Ouyang et al Cell Death and Disease (2020)11:486. Male 41 Male 47 Female 47 Female 27 Male 46 Male 48 Female 58 Male 33 Male 21 Male 25 Female 44 Male 45 Male 58 Male 24 Male 42 Male 44 Female 58 Female 25 Male 26 Male 25 Female 22 Male 24 Male 48 Male 31

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