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KMID : 1204720220150030334
International Journal of Stem Cells
2022 Volume.15 No. 3 p.334 ~ p.345
Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4¡¯-Dihydroxyflavone, U0126, and N-Acetyl Cysteine
Song Kwon-Woo

Yang Gwang-Mo
Han Ji-Hae
Gil Min-Chan
Dayem Ahmed Abdal
Kim Kyeong-Seok
Lim Kyung-Min
Kang Geun-Ho
Kim Se-Jong
Jang Soo-Bin
Vellingiri Balachandar
Cho Ssang-Goo
Abstract
Background and Objectives: Flavonoids form the largest group of plant phenols and have various biological and pharmacological activities. In this study, we investigated the effect of a flavonoid, 3, 4¡¯-dihydroxyflavone (3, 4¡¯-DHF) on osteogenic differentiation of equine adipose-derived stromal cells (eADSCs).

Methods and Results: Treatment of 3, 4¡¯-DHF led to increased osteogenic differentiation of eADSCs by increasing phosphorylation of ERK and modulating Reactive Oxygen Species (ROS) generation. Although PD98059, an ERK inhibitor, suppressed osteogenic differentiation, another ERK inhibitor, U0126, apparently increased osteogenic differentiation of the 3, 4¡¯-DHF-treated eADSCs, which may indicate that the effect of U0126 on bone morphogenetic protein signaling is involved in the regulation of 3, 4¡¯-DHF in osteogenic differentiation of eADSCs. We revealed that 3, 4¡¯-DHF could induce osteogenic differentiation of eADSCs by suppressing ROS generation and co-treatment of 3, 4¡¯-DHF, U0126, and/or N-acetyl cysteine (NAC) resulted in the additive enhancement of osteogenic differentiation of eADSCs.

Conclusions: Our results showed that co-treatment of 3, 4¡¯-DHF, U0126, and/or NAC cumulatively regulated osteogenesis in eADSCs, suggesting that 3, 4¡¯-DHF, a flavonoid, can provide a novel approach to the treatment of osteoporosis and can provide potential therapeutic applications in therapeutics and regenerative medicine for human and companion animals.
KEYWORD
3, 4¡¯-dihydroxyflavone, Osteogenesis, Equine adipose-derived stromal cells, Regenerative medicine
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