Selenium Nanoparticles by Moderating Oxidative Stress Promote Differentiation of Mesenchymal Stem Cells to Osteoblasts
Received 7 October 2020
Accepted for publication 27 November 2020
Published 13 January 2021 Volume 2021:16 Pages 331—343
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Thomas J. Webster
Sabiha Fatima,1 Rawan Alfrayh,1 May Alrashed,2 Sarah Alsobaie,1 Rehan Ahmad,3 Amer Mahmood4
1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia; 2Chair of Medical and Molecular Genetics Research, Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh 11433, Saudi Arabia; 3Colorectal Research Chair, Department of Surgery, King Saud University, College of Medicine, Riyadh 11472, Saudi Arabia; 4Stem Cell Unit, Department of Anatomy, College of Medicine, King Khalid University Hospital, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia
Correspondence: Sabiha Fatima
Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, King Saud University, Riyadh, Saudi Arabia
Stem Cell Unit, Department of Anatomy, College of Medicine, King Saud University, Riyadh 11461, Kingdom of Saudi Arabia
Purpose: Redox homeostasis plays an important role in the osteogenic differentiation of human mesenchymal stem cells (hMSCs) for bone engineering. Oxidative stress (OS) is believed to induce osteoporosis by changing bone homeostasis. Selenium nanoparticles (SeNPs), an antioxidant with pleiotropic pharmacological activity, prevent bone loss. However, the molecular mechanism underlying the osteogenic activity during hMSC–SeNP interaction is unclear.
Methods: This study assessed the effects of different concentrations (25, 50, 100, and 300 ng/mL) of SeNPs on the cell viability and differentiation ability of human embryonic stem cell-derived hMSCs. In addition, we analyzed OS markers and their effect on mitogen-activated protein kinase (MAPK) and Forkhead box O3 (FOXO3) during osteogenesis.
Results: SeNPs increased the cell viability of hMSCs and induced their differentiation toward an osteogenic over an adipogenic lineage by enhancing osteogenic transcription and mineralization, while inhibiting Nile red staining and adipogenic gene expression. By preventing excessive reactive oxygen species accumulation, SeNPs increased antioxidant levels in hMSCs undergoing osteogenesis compared to untreated cells. In addition, SeNPs significantly upregulated the gene and protein expression of phosphorylated c-Jun N-terminal kinase (JNK) and FOXO3a, with no significant change in the expression levels of extracellular signal-related kinase (ERK) and p38 MAPK.
Conclusion: The results approved that low concentrations of SeNPs might enhance the cell viability and osteogenic potential of hMSCs by moderating OS. Increased JNK and FOXO3a expression shows that SeNPs might enhance osteogenesis via activation of the JNK/FOXO3 pathway. In addition, SeNP co-supplementation might prevent bone loss by enhancing osteogenesis and, thus, can be an effective candidate for treating osteoporosis through cell-based therapy.
Keywords: selenium nanoparticles stem cells, antioxidant, osteogenic differentiation