The effects of Gli1 and Gli2 on BMP9-induced osteogenic differentiation of mesenchymal stem cells

Tissue Cell. 2023 Oct:84:102168. doi: 10.1016/j.tice.2023.102168. Epub 2023 Jul 17.

Abstract

Diseases, such as bone nonunion with bone defects, osteoporosis, etc, seriously endanger people's quality of life, and bone tissue engineering based on mesenchymal stem cells is an effective method to solve such problems. Several studies have shown that BMP9 can effectively promote osteogenic differentiation of MSCs, but the underlying molecular mechanisms are still unclear. Gli1 and Gli2 were important transcription factors and play an important role in the Hedgehog signaling pathway. In this study, we investigated the role of Gli1 and Gli2 in BMP9-induced osteogenic differentiation of MSCs. We found that inhibition of Gli1 and Gli2 weakened BMP9-induced osteogenic differentiation of MSCs, and early osteogenic markers (alkaline phosphatase, ALP), late osteogenic markers (calcium salt deposition), the expression of pivotal osteogenic markers were attenuated, and inhibition of Gli1 and Gli2 weakened the expression of p-Smad1/5/8 and p-p38 induced by BMP9. In conclusion, our study shows that Gli1 and Gli2 play an important role in BMP9-induced osteogenic differentiation.

Keywords: BMP9; Hedgehog; Mesenchymal stem cells; Signal Transduction.

MeSH terms

  • Animals
  • Cell Differentiation
  • Growth Differentiation Factor 2 / metabolism
  • Growth Differentiation Factor 2 / pharmacology
  • Hedgehog Proteins / metabolism
  • Hedgehog Proteins / pharmacology
  • Mesenchymal Stem Cells*
  • Mice
  • Osteogenesis*
  • Quality of Life
  • Zinc Finger Protein GLI1* / genetics
  • Zinc Finger Protein GLI1* / metabolism
  • Zinc Finger Protein GLI1* / pharmacology
  • Zinc Finger Protein Gli2*

Substances

  • Gli2 protein, mouse
  • Growth Differentiation Factor 2
  • Hedgehog Proteins
  • Zinc Finger Protein GLI1
  • Zinc Finger Protein Gli2