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Published on: May 4, 2018
FTY720 enhances osteogenic differentiation of bone marrow mesenchymal stem cells in ovariectomized rats
Chuang Huang1, Rui Ling2, Fei-Jiang Li3
1Department of Orthodontics, State Key Laboratory of Military Stomatology, School of Stomatology, The Fourth Military Medical University, Xi'an, Shaanxi 710032, P.R. China.
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.
Insights
FTY720 (fingolimod) significantly enhances bone formation by upregulating key osteogenic markers in bone marrow mesenchymal stem cells. This suggests FTY720 as a potential therapy for preventing bone loss in osteoporosis.
Area of Science:
- Bone Biology and Regenerative Medicine
- Stem Cell Differentiation
- Pharmacology
Background:
- Sphingosine-1-phosphate and FTY720 (fingolimod) are known to inhibit osteoclast activity.
- Their role in promoting osteogenic differentiation of bone marrow mesenchymal stem cells (BM-MSCs) is not well understood.
Purpose of the Study:
- To investigate the effect of FTY720 on the osteogenic differentiation of BM-MSCs.
- To assess FTY720's potential as a therapeutic agent for bone loss in ovariectomized (OVX) rats.
Main Methods:
- BM-MSCs were isolated from OVX rats.
- Cells were treated with three different concentrations of FTY720 (1, 10, and 100 nM).
- mRNA and protein expression of key osteogenic markers (Runx2, Sp7, ALP, OCN) were analyzed at 2 and 3 weeks.
Main Results:
- FTY720 markedly upregulated mRNA expression of Runx2 and Sp7 at 2 weeks, and ALP at 3 weeks.
- Protein levels of Runx2, Sp7, OCN, and ALP were significantly increased by FTY720 in both OVX and sham groups at 3 weeks.
- Osteocalcin expression showed similar levels at weeks 2 and 3.
Conclusions:
- FTY720 demonstrates a beneficial effect on bone formation in OVX rats.
- FTY720 holds potential as a therapeutic strategy to prevent alveolar bone resorption in post-menopausal osteoporosis.
