Circ_0067680 expedites the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells through miR-4429/CTNNB1/Wnt/β-catenin pathway

Biol Direct. 2021 Oct 14;16(1):16. doi: 10.1186/s13062-021-00302-w.

Abstract

Background: Human bone marrow-derived mesenchymal stem cells (hBMSCs) are the primary source of osteoblasts in vivo. Emerging literatures have unveiled that circular RNAs (circRNAs) are actively drawn in the osteogenic differentiation of mesenchymal stem cells (MSCs). This research mainly illuminated the role of circ_0067680 as well as its regulatory mechanism in osteoblastic differentiation.

Methods: In this study, RT-qPCR was to measure the expression of circ_0067680. Functional assays were implemented to assess the role of circ_0067680 in osteogenic differentiation. Besides, RNA pull down, RIP and luciferase reporter assays were carried out to investigate the regulatory mechanism of circ_0067680.

Results: Circ_0067680, which derived from its host gene divergent protein kinase domain 2A (C3orf58), was up-regulated during osteogenic differentiation of hBMSCs. Besides, circ_0067680 deficiency impeded the osteoblastic differentiation of hBMSCs. Moreover, circ_0067680 served as a ceRNA via sequestering miR-4429 to regulate the expression of catenin beta 1 (CTNNB1), thereby activating the Wnt/β-catenin signaling pathway.

Conclusion: Circ_0067680 accelerated hBMSCs osteogenic differentiation by the miR-4429/CTNNB1/Wnt/β-catenin signaling, which might be used as a potential biomarker for osteoblastic differentiation.

Keywords: CTNNB1; Osteogenic differentiation; Wnt/β-catenin signaling pathway; circ_0067680; miR-4429.

MeSH terms

  • Bone Marrow / metabolism
  • Cell Differentiation
  • Humans
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • Osteogenesis / genetics
  • Wnt Signaling Pathway / genetics
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • MicroRNAs
  • beta Catenin