Long Noncoding RNA DANCR Is a Positive Regulator of Proliferation and Chondrogenic Differentiation in Human Synovium-Derived Stem Cells

DNA Cell Biol. 2017 Feb;36(2):136-142. doi: 10.1089/dna.2016.3544. Epub 2016 Dec 16.

Abstract

Cartilage tissues have limited capacity for repair after damage and then cause osteoarthritis, so finding alternative treatment is ongoing. Mesenchymal stem cells (MSCs) have become a promising therapy for cartilage damage and diseases due to the advantages of easy separation, high proliferative potentiality, and genetic stability. Synovium-derived MSCs (SMSCs) have been recognized as an ideal source for cartilage repair. In our previous study, we found that Sox4 promoted proliferation and chondrogenesis of SMSCs through upregulation of long noncoding RNA (lncRNA) DANCR. However, the exact molecular mechanism by which DANCR promotes proliferation and chondrogenesis of SMSCs remains unknown. In the present study, we investigated the effect of lncRNA DANCR on the proliferation and chondrogenesis of SMSCs. We found that overexpression of DANCR could promote proliferation and chondrogenesis of SMSCs, while knockdown of DANCR had the opposite effect. Moreover, our data demonstrated that DANCR directly interacted with myc, Smad3, and STAT3 mRNA to regulate their stability. Finally, we found that the promotion of SMSC proliferation induced by DANCR depended on myc. Also, DANCR activated chondrogenesis of SMSCs via upregulation of Smad3 and STAT3 expression. Our growing knowledge of the role of DANCR is pointing toward its potential use as a novel therapeutic approach for cartilage damage and diseases.

Keywords: DANCR; STAT3; Smad3; chondrogenic differentiation; myc; synovium-derived stem cell.

MeSH terms

  • Base Sequence
  • Cell Differentiation / genetics*
  • Cell Proliferation / genetics
  • Chondrogenesis / genetics*
  • Gene Knockdown Techniques
  • Humans
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Proto-Oncogene Proteins c-myc / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • STAT3 Transcription Factor / genetics
  • Smad3 Protein / genetics
  • Synovial Membrane / cytology*
  • Up-Regulation / genetics

Substances

  • Proto-Oncogene Proteins c-myc
  • RNA, Long Noncoding
  • RNA, Messenger
  • STAT3 Transcription Factor
  • Smad3 Protein