Exendin‑4 promotes osteogenic differentiation of adipose‑derived stem cells and facilitates bone repair

Mol Med Rep. 2019 Dec;20(6):4933-4942. doi: 10.3892/mmr.2019.10764. Epub 2019 Oct 23.

Abstract

Inflammation‑related bone defects pose a heavy burden on patients and orthopedic surgeons. Although stem‑cell‑based bone repair has developed rapidly, it is of great significance to characterize bio‑active molecules that facilitate bone regeneration. It is reported that a glucagon‑like peptide 1 receptor agonist, exendin‑4, promoted bone regeneration mediated by the transplantation of adipose‑derived stem cells in a metaphyseal defect mouse model of femur injury. However, the underlying mechanism is unclear. Bone imaging, immunohistochemistry real‑time PCR and western blot analysis were used in the present study, and the results revealed that exendin‑4 increased the transcription of the osteogenic differentiation‑related genes and induced osteogenic differentiation in situ. Furthermore, the present data obtained from sorted adipose‑derived stem cells revealed that exendin‑4 promoted osteogenic differentiation and inhibited adipogenic differentiation in vitro. These findings indicated that exendin‑4 facilitates osteogenic differentiation of transplanted adipose‑derived stem cells for bone repair and illuminated clinical prospects of both adipose‑derived stem cells and exendin‑4 in stem‑cell‑based bone defect repair.

MeSH terms

  • Animals
  • Bone Regeneration / drug effects*
  • Cells, Cultured
  • Exenatide / pharmacology
  • Exenatide / therapeutic use*
  • Femur / drug effects
  • Femur / injuries
  • Femur / metabolism
  • Femur / pathology
  • Glucagon-Like Peptide-1 Receptor / agonists*
  • Male
  • Mesenchymal Stem Cell Transplantation
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice, Inbred C57BL
  • Osteogenesis / drug effects*
  • Transcriptional Activation / drug effects

Substances

  • Glucagon-Like Peptide-1 Receptor
  • Exenatide