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In vitro Evaluation of Ferutinin on Proliferation and Osteogenesis differentiation in Human Unrestricted Somatic Stem Cells

Zahra Mahmoudi 1Abbas Saidi 2Mehrdad Iranshahi 3Neda Dadgar 4Arezou Azizsoltani 5Sahar Behzad 6Ladan Mahmoudi 7Masoud Soleimani 8Hamed Parsa Khankandi 9

Steroids doi: 10.1016/j.steroids.2021.108862. 

Abstract

Osteoporosis is a common disease in post-menopausal women. The increased risk of breast cancer and malignancy with hormone replacement, hampers its wide-usage. Phytoestrogens are known to have selective estrogen receptor modulator activity. The present study aims to determine how ferutinin affects unrestricted human Somatic Stem Cells (USSCs) osteogenic differentiation. The effect of ferutinin on USSCs proliferation was assessed by MTT assay while osteogenesis was evaluated using Alkaline Phosphatase Activity (ALP), calcium deposition and Alizarin Red Staining. Quantitative real-time PCR was applied to examine the expression of bone specific genes such as osteocalcin, Runx2, and BMP-2. Ferutinin (5 to 15 µg/mL) could positively impact on the proliferation of cells in a dose-dependent manner. Also, ALP enzyme activity and calcium deposition were enhanced in the presence of ferutinin. Based on real-time PCR results, ferutinin could increase the expression of bone marker genes. The pattern of ferutinin effect on gene expression is similar to standard synthetic estrogen, 17-β-estradiol. In the presence of the estrogen activity inhibitor (ICI), the effect of ferutinin on ALP and gene level was diminished. In conclusion, ferutinin may be considered as a potential candidate for the stem cell therapy in osteoporosis. Key world:Osteogenesis, Ferutinin, Ferula species, Osteoporosis, Human Unrestricted Somatic Stem Cells.