Long non-coding RNA DANCR modulates osteogenic differentiation by regulating the miR-1301-3p/PROX1 axis

Mol Cell Biochem. 2021 Jun;476(6):2503-2512. doi: 10.1007/s11010-021-04074-9. Epub 2021 Feb 24.

Abstract

The balance of osteoblasts and marrow adipocytes from bone marrow mesenchymal stem cells (BM-MSCs) maintains bone health. Under aging or other pathological stimuli, BM-MSCs will preferentially differentiate into marrow adipocytes and reduce osteoblasts, leading to osteoporosis. Long non-coding RNA differentiation antagonizing non-protein coding RNA (DANCR) participates in the osteogenic differentiation of human BM-MSCs, but the mechanism by which DANCR regulates the osteogenic differentiation of human BM-MSCs has not been fully explained. We observed that DANCR and prospero homeobox 1 (PROX1) were downregulated during osteogenic differentiation of human BM-MSCs, while miR-1301-3p had an opposite trend. DANCR overexpression decreased the levels of alkaline phosphatase, RUNX2, osteocalcin, Osterix in BM-MSCs after osteogenic induction, but DANCR silencing had the opposite result. Moreover, DANCR sponged miR-1301-3p to regulate PROX1 expression. miR-1301-3p overexpression reversed the suppressive role of DANCR elevation on the osteogenic differentiation of human BM-MSCs. Also, PROX1 elevation abolished the promoting role of miR-1301-3p overexpression on the osteogenic differentiation of human BM-MSCs. In conclusion, DANCR suppressed the osteogenic differentiation of human BM-MSCs through the miR-1301-3p/PROX1 axis, offering a novel mechanism by which DANCR is responsible for the osteogenic differentiation of human BM-MSCs.

Keywords: BM-MSCs; DANCR; OP; PROX1; miR-1301-3p.

MeSH terms

  • Bone Marrow Cells / metabolism*
  • Cell Differentiation*
  • Cell Line
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mesenchymal Stem Cells / metabolism*
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Osteogenesis*
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction*
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*

Substances

  • DANCR long noncoding RNA, human
  • Homeodomain Proteins
  • MIRN1301 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Tumor Suppressor Proteins
  • prospero-related homeobox 1 protein