Circ_0006873 suppresses the osteogenic differentiation of human-derived mesenchymal stem cells through mediating miR-20a/SMURF2 axis in vitro

APMIS. 2023 Jul;131(7):313-324. doi: 10.1111/apm.13321. Epub 2023 Apr 27.

Abstract

The clinical application of human-derived mesenchymal stem cells (hMSCs) in osteoporosis (OP) treatment is promising. We aimed to uncover the role of circular RNA 0006873 (circ_0006873) in OP progression using hMSCs. The levels of circ_0006873, pantothenate kinase 2 (PANK2) messenger RNA (mRNA), microRNA-20a (miR-20a), SMAD specific E3 ubiquitin protein ligase 2 (SMURF2) mRNA and the mRNA levels of osteogenesis-related markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of osteogenesis-related markers and SMURF2 was detected by Western blot assay. Alkaline phosphatase (ALP) staining and activity were determined using an ALP staining Kit and an ALP Colorimetric Assay Kit. Circ_0006873 was highly expressed in the serum samples and bone tissue samples of OP patients compared with control cases. Circ_0006873 overexpression down-regulated the expression of osteogenesis-related markers and reduced ALP staining and activity. Circ_0006873 down-regulated miR-20a level through its interaction with miR-20a in hMSCs. Circ_0006873 suppressed osteogenic differentiation through targeting miR-20a. SMURF2 was a molecular target of miR-20a, and miR-20a promoted osteogenic differentiation through targeting SMURF2. Circ_0006873 suppressed the osteogenic differentiation of hMSCs by upregulating SMURF2 level via sponging miR-20a in vitro.

Keywords: Osteoporosis; SMURF2; circ_0006873; miR-20a; osteogenic differentiation.

MeSH terms

  • Cell Differentiation / genetics
  • Cells, Cultured
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / metabolism
  • Osteogenesis / genetics
  • Osteoporosis* / genetics
  • Osteoporosis* / metabolism
  • RNA, Messenger / metabolism
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism

Substances

  • MicroRNAs
  • RNA, Messenger
  • SMURF2 protein, human
  • Ubiquitin-Protein Ligases