Long noncoding RNA AC092155 facilitates osteogenic differentiation of adipose-derived stem cells through the miR-143-3p/STMN1 axis

J Gene Med. 2021 Aug;23(8):e3363. doi: 10.1002/jgm.3363. Epub 2021 Jun 1.

Abstract

Background: Numerous studies have demonstrated that long noncoding RNAs (lncRNAs) induce osteogenesis in adipose-derived stem cells (ADSCs). This study aimed to explore the role of lncRNAs AC092155 in promoting osteogenic differentiation of ADSCs.

Methods: MicroRNA (miRNA) and lncRNA sequencing were performed in ADSCs that underwent normal or osteogenic induction. Differentially expressed miRNAs and lncRNAs were identified using R software. The relative expression levels of lncRNA AC092155, miR-143-3p, and STMN1 during the process of osteogenic induction were determined by real-time polymerase chain reaction (RT-PCR). ADSCs were then transfected with agomiR-143-3p and pcDNA3.1-sh-lncRNA AC092155. Alkaline phosphatase (ALP) and alizarin red staining (ARS) were used to confirm the regulatory function of the lncRNA AC092155/miR-143-3p/STMN1 axis in osteogenic differentiation of ADSCs.

Results: lncRNA AC092155 was significantly upregulated in ADSCs following induction in the osteogenic medium. lncRNA AC092155 and STMN1 mimics increase the markers of osteogenic differentiation in the early and late phases, which was reflected in increased ALP activity as well as the higher deposition of calcium nodules. An miR-143-3p mimic showed the opposite effect. Luciferase reporter gene analysis demonstrated that lncRNA AC092155 directly targets miR-143-3p. Moreover, the lncRNA AC092155/miR-143-3p/STMN1 regulatory axis was found to activate the Wnt/β-catenin signaling pathway.

Conclusions: lncRNA AC092155 contributes to the osteogenic differentiation of ADSCs. The lncRNA AC092155/miR-143-3p/STMN1 axis may be a new therapeutic target for bone-related diseases.

Keywords: ADSCs; STMN1; lncRNA AC092155; miR-143-3p; osteogenic differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Cell Differentiation / genetics
  • Cells, Cultured
  • Gene Expression Regulation
  • Humans
  • Osteogenesis / genetics*
  • RNA, Long Noncoding / genetics*
  • Stathmin / genetics*
  • Stem Cells / cytology*
  • Stem Cells / physiology
  • Up-Regulation

Substances

  • RNA, Long Noncoding
  • STMN1 protein, human
  • Stathmin