The LncRNA ZBED3-AS1 induces chondrogenesis of human synovial fluid mesenchymal stem cells

Biochem Biophys Res Commun. 2017 May 27;487(2):457-463. doi: 10.1016/j.bbrc.2017.04.090. Epub 2017 Apr 18.

Abstract

Human synovial fluid-derived mesenchymal stem cells (SFMSCs) have great potential for cartilage induction and are promising for cell-based strategies for articular cartilage repair. Many long non-coding RNAs (lncRNAs) regulate chondrogenesis of MSCs. We hypothesized that the divergent lncRNA ZBED3-AS1, which binds locally to chromatin, could promote the expression of zbed3, a novel Axin-interacting protein that activates Wnt/β-catenin signaling, involved in chondrogenesis. However, the function of ZBED3-AS1 in SFMSCs is unclear. In this study, the expression, biological function, and roles of ZBED3-AS1 in SFMSC chondrogenesis were examined by multilineage differentiation, flow cytometry, and gain-of-function studies. We found that ZBED3-AS1 promotes chondrogenesis. Furthermore, ZBED3-AS1 could directly increase zbed3 expression. Finally, the wnt-inhibitor DKK1 could reverse the stimulatory effect of ZBED3-AS1 on chondrogenesis. These findings demonstrate the role of a new lncRNA, ZBED3-AS1, in SFMSC chondrogenesis and may improve osteoarthritis treatment.

Keywords: Human synovial fluid-derived mesenchymal stem cell; ZBED3-AS1; lncRNA.

MeSH terms

  • Cell Differentiation / physiology
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / metabolism
  • Chondrogenesis / physiology*
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Synovial Fluid / cytology*
  • Synovial Fluid / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • DNA-Binding Proteins
  • RNA, Long Noncoding
  • Transcription Factors
  • ZBED3 protein, human