Journal
STEM CELL RESEARCH & THERAPY
Volume 8, Issue -, Pages -Publisher
BIOMED CENTRAL LTD
DOI: 10.1186/s13287-017-0726-8
Keywords
Strontium; Human adipose-derived mesenchymal stem cells; Osteogenesis; ERK1/2 signaling pathway
Funding
- National Natural Science Foundation of China [81303065, 81471798]
- National Natural Science Foundation of China-Xinjiang joint fund [U1503221]
- Major projects in the Xinjiang Uygur Autonomous Region [201430123-3]
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Background: Strontium is a widely used anti-osteoporotic agent due to its dual effects on inhibiting bone resorption and stimulating bone formation. Thus, we studied the dose response of strontium on osteo-inductive efficiency in human adipose-derived stem cells (hASCs). Method: Qualitative alkaline phosphatase (ALP) staining, quantitative ALP activity, Alizarin Red staining, real-time polymerase chain reaction and Western blot were used to investigate the in vitro effects of a range of strontium concentrations on hASC osteogenesis and associated signaling pathways. Results: In vitro work revealed that strontium (25-500 mu M) promoted osteogenic differentiation of hASCs according to ALP activity, extracellular calcium deposition, and expression of osteogenic genes such as runt-related transcription factor 2, ALP, collagen-1, and osteocalcin. However, osteogenic differentiation of hASCs was significantly inhibited with higher doses of strontium (1000-3000 mu M). These latter doses of strontium promoted apoptosis, and phosphorylation of ERK1/2 signaling was increased and accompanied by the downregulation of Bcl-2 and increased phosphorylation of BAX. The inhibition of ERK1/2 decreased apoptosis in hASCs. Conclusion: Lower concentrations of strontium facilitate osteogenic differentiation of hASCs up to a point; higher doses cause apoptosis of hASCs, with activation of the ERK1/2 signaling pathway contributing to this process.
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