FTY720 enhances osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomized rats

Mol Med Rep. 2016 Jul;14(1):927-35. doi: 10.3892/mmr.2016.5342. Epub 2016 May 24.

Abstract

Sphingosine-1-phosphate and its structural analog FTY720 (fingolimod) are important in the inhibition of osteoclast differentiation and bone resorption, however, it remains unknown whether they enhance osteogenic differentiation of the bone marrow mesenchymal stem cells (BM‑MSCs). The present study investigated the effect of FTY720 on the osteogenic differentiation of BM‑MSCs from the femurs of the ovariectomized (OVX) rats. Three different concentrations (1, 10 and 100 nM) of FTY720 were demonstrated to markedly upregulate mRNA expression levels of Runt‑related transcription factor 2 (Runx2) and Sp7 transcription factor (Sp7) at 2 weeks, and alkaline phosphatase (ALP) at 3 weeks. The osteocalcin (OCN) expression was similar at weeks 2 and 3. The protein expression levels of Runx2, Sp7, OCN and ALP induced by three different concentrations of FTY720 were higher than those in the control groups at 3 weeks in the OVX and sham groups. The findings of the current study suggested a beneficial effect of FTY720 on bone formation in OVX rats, and provided a potential therapeutic method of FTY720 to prevent alveolar bone resorption in patients with post‑menopausal osteoporosis.

MeSH terms

  • Animals
  • Antigens, CD / metabolism
  • Biomarkers
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / drug effects
  • Bone and Bones / metabolism
  • Bone and Bones / pathology
  • Cell Differentiation / drug effects*
  • Cell Self Renewal / drug effects
  • Cell Self Renewal / genetics
  • Female
  • Fingolimod Hydrochloride / pharmacology*
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects
  • Immunophenotyping
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Osteogenesis / drug effects*
  • Osteogenesis / genetics
  • Osteoporosis / diagnostic imaging
  • Osteoporosis / etiology
  • Osteoporosis / metabolism
  • Osteoporosis / pathology
  • Ovariectomy
  • Rats

Substances

  • Antigens, CD
  • Biomarkers
  • Fingolimod Hydrochloride