Characterization of exosomal long non-coding RNAs in chondrogenic differentiation of human adipose-derived stem cells

Mol Cell Biochem. 2021 Mar;476(3):1411-1420. doi: 10.1007/s11010-020-04003-2. Epub 2021 Jan 3.

Abstract

The exosomes derived from chondrogenic stem cells and long non-coding RNAs (lncRNAs) play a key role in cartilage regeneration. Here, we investigated the expression profile of exosomal lncRNAs in chondrogenesis of human adipose derived stem cells (hADSCs). hADSCs were induced to differentiate into chondrocytes in vitro. Exosomes from undifferentiated hADSCs and chondrogenic hADSCs were isolated. LncRNA and mRNA expression profiles in the isolated exosomes were analyzed by RNA sequencing. The resultant data were subjected to gene ontology (GO) terms and KEGG pathway analysis to identify differentially expressed lncRNAs. We identified 23 upregulated and 163 downregulated lncRNAs in exosomes derived from chondrogenic hADSCs compared to that in exosomes from undifferentiated hADSCs. In addition, analysis of mRNA expression data revealed 968 upregulated genes and 572 downregulated genes in exosomes of chondrogenic hADSCs. Lncrna and mRNA expression levels were further validated by qRT-PCR. Differentially expressed lncRNAs and mRNAs were utilized to construct a coding-non-coding gene co-expression network (CNC network). GO terms and KEGG pathway enrichment analysis revealed several significant processes differentially regulated between undifferentiated hADSCs and chondrogenic hADSCs. Taken together, this study revealed the differential expression of exosomal lncRNAs of chondrogenic hADSCs and provided a foundation for future study on the cartilage recovery mechanism of exosomes derived from chondrogenic stem cells.

Keywords: Chondrogenesis; Exosomes; LncRNAs.

MeSH terms

  • Adipocytes / metabolism
  • Adipose Tissue / cytology*
  • Cartilage / pathology
  • Cell Differentiation*
  • Cells, Cultured
  • Chondrocytes / cytology*
  • Chondrogenesis
  • Exosomes / metabolism*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Regulatory Networks
  • Humans
  • MicroRNAs / genetics
  • RNA, Long Noncoding*
  • RNA, Messenger / metabolism
  • Sequence Analysis, RNA
  • Stem Cells / cytology

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger