Shuanglongjiegu pill promoted bone marrow mesenchymal stem cell osteogenic differentiation by regulating the miR-217/RUNX2 axis to activate Wnt/β-catenin pathway

J Orthop Surg Res. 2024 Oct 1;19(1):617. doi: 10.1186/s13018-024-05085-0.

Abstract

This study aimed to investigate the effects of Shuanglongjiegu pill (SLJGP) on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and explore its mechanism based on miR-217/RUNX2 axis. Results found that drug-containing serum of SLJGP promoted BMSCs viability with a dose-dependent effect. Under osteogenic differentiation conditions, SLJGP promoted the expression of ALP, OPN, BMP2, RUNX2, and the osteogenic differentiation ability of BMSCs. In addition, SLJGP significantly reduced miR-217 expression, and miR-217 directly targeted RUNX2. After treatment with miR-217 mimic, the promoting effects of SLJGP on proliferation and osteogenic differentiation of BMSCs were significantly inhibited. MiR-217 mimic co-treated with pcDNA-RUNX2 further confirmed that the miR-217/RUNX2 axis was involved in SLJGP to promote osteogenic differentiation of BMSCs. In addition, analysis of Wnt/β-catenin pathway protein expression showed that SLJGP activated the Wnt/β-catenin pathway through miR-217/RUNX2. In conclusion, SLJGP promoted osteogenic differentiation of BMSCs by regulating miR-217/RUNX2 axis and activating Wnt/β-catenin pathway.

Keywords: Bone marrow mesenchymal stem cells; Osteogenic differentiation; Shuanglongjiegu pill; Traditional Chinese medicine; Wnt/β-catenin pathway; miR-217/RUNX2 axis.

MeSH terms

  • Animals
  • Bone Marrow Cells / drug effects
  • Bone Marrow Cells / metabolism
  • Cell Differentiation* / drug effects
  • Cell Differentiation* / genetics
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit* / genetics
  • Core Binding Factor Alpha 1 Subunit* / metabolism
  • Drugs, Chinese Herbal* / pharmacology
  • Humans
  • Mesenchymal Stem Cells* / drug effects
  • Mesenchymal Stem Cells* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Osteogenesis* / drug effects
  • Osteogenesis* / genetics
  • Wnt Signaling Pathway* / drug effects
  • Wnt Signaling Pathway* / genetics
  • Wnt Signaling Pathway* / physiology

Substances

  • MicroRNAs
  • Core Binding Factor Alpha 1 Subunit
  • Drugs, Chinese Herbal
  • MIRN217 microRNA, human
  • RUNX2 protein, human