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International journal of stem cells2022; 15(3); 334-345; doi: 10.15283/ijsc22044

Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4′-Dihydroxyflavone, U0126, and N-Acetyl Cysteine.

Abstract: 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). Unassigned: 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. Unassigned: 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.
Publication Date: 2022-06-30 PubMed ID: 35769058PubMed Central: PMC9396012DOI: 10.15283/ijsc22044Google Scholar: Lookup
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  • Journal Article

Summary

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This research investigated the impact of a flavonoid called 3, 4′-Dihydroxyflavone (3, 4′-DHF) on the bone formation process in equine adipose-derived stromal cells (eADSCs). The study’s results suggest that 3, 4′-DHF can aid in osteogenesis, potentially offering novel treatment possibilities for osteoporosis.

Research Objectives and Methodology

  • The main objective of this study was to investigate the effect of a specific flavonoid, 3, 4′-Dihydroxyflavone (3, 4′-DHF), on osteogenic differentiation in equine adipose-derived stromal cells (eADSCs). Osteogenic differentiation is the process where cells develop into bone-forming cells.
  • This particular type of flavonoid was chosen due to the known biological and pharmacological properties of flavonoids, a large group of plant phenols.
  • The researchers employed in vitro testing, treating eADSCs with 3, 4′-DHF, and monitoring changes in ERK phosphorylation and Reactive Oxygen Species (ROS) generation, both important factors in bone formation.

Findings of the Research

  • The research revealed that treatment with 3, 4′-DHF enhanced the osteogenic differentiation in eADSCs by increasing the phosphorylation of ERK and regulating the generation of ROS.
  • When the researchers used PD98059, an ERK inhibitor, they noted that osteogenic differentiation was suppressed. Interestingly, a different ERK inhibitor, U0126, seemed to enhance osteogenic differentiation when used in combination with 3, 4′-DHF-treated eADSCs. These findings suggest that the specific influence of U0126 on bone morphogenetic protein signaling may be involved in 3, 4′-DHF’s regulation of osteogenic differentiation in eADSCs.
  • The researchers also found that 3, 4′-DHF was capable of inducing osteogenic differentiation by suppressing ROS generation. Additionally, the simultaneous treatment of eADSCs with 3, 4′-DHF, U0126, and N-acetyl cysteine (NAC), an antioxidant, led to further improvements in osteogenic differentiation.

Conclusions and Implications

  • The study concluded that the co-treatment of eADSCs with 3, 4′-DHF, U0126, and NAC synergistically promoted osteogenesis.
  • These findings suggest that 3, 4′-DHF, a flavonoid, could potentially offer a new approach to the treatment of osteoporosis, by encouraging the formation of bone cells.
  • Such a development could have significant potential applications in therapeutics and regenerative medicine, for both human and veterinary care, particularly in the effective treatment of bone diseases and injuries.

Cite This Article

APA
Song K, Yang GM, Han J, Gil M, Dayem AA, Kim K, Lim KM, Kang GH, Kim S, Jang SB, Vellingiri B, Cho SG. (2022). Modulation of Osteogenic Differentiation of Adipose-Derived Stromal Cells by Co-Treatment with 3, 4′-Dihydroxyflavone, U0126, and N-Acetyl Cysteine. Int J Stem Cells, 15(3), 334-345. https://doi.org/10.15283/ijsc22044

Publication

ISSN: 2005-3606
NlmUniqueID: 101497587
Country: Korea (South)
Language: English
Volume: 15
Issue: 3
Pages: 334-345

Researcher Affiliations

Song, Kwonwoo
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Yang, Gwang-Mo
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Han, Jihae
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Gil, Minchan
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Dayem, Ahmed Abdal
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Kim, Kyeongseok
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Lim, Kyung Min
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Kang, Geun-Ho
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Kim, Sejong
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Jang, Soo Bin
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.
Vellingiri, Balachandar
  • Human Molecular Cytogenetics and Stem Cell Laboratory, Department of Human Genetics and Molecular Biology, Bharathiar University, Coimbatore, India.
Cho, Ssang-Goo
  • Department of Stem Cell and Regenerative Biotechnology and Incurable Disease Animal Model and Stem Cell Institute (IDASI), Konkuk University, Seoul, Korea.

Conflict of Interest Statement

. The authors have no conflicting financial interest.

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Citations

This article has been cited 1 times.
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