Green tea polyphenol EGCg induces cell fusion via reactive oxygen species

Background: Osteoclasts are multinucleated cells formed by macrophage cell fusion that are responsible for bone resorption. Previously, we found that treating osteoclastic progenitor cells with (−)-epigallocatechin gallate (EGCg) increased cell fusion. In this study, we aimed to identify factors inv...

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Main Authors: Kenji Kuriya, Shimon Itoh, Akihiro Isoda, Shoki Tanaka, Masahiro Nishio, Hayato Umekawa
Format: Article
Language:English
Published: Elsevier 2023-09-01
Series:Biochemistry and Biophysics Reports
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S2405580823001176
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author Kenji Kuriya
Shimon Itoh
Akihiro Isoda
Shoki Tanaka
Masahiro Nishio
Hayato Umekawa
author_facet Kenji Kuriya
Shimon Itoh
Akihiro Isoda
Shoki Tanaka
Masahiro Nishio
Hayato Umekawa
author_sort Kenji Kuriya
collection DOAJ
description Background: Osteoclasts are multinucleated cells formed by macrophage cell fusion that are responsible for bone resorption. Previously, we found that treating osteoclastic progenitor cells with (−)-epigallocatechin gallate (EGCg) increased cell fusion. In this study, we aimed to identify factors involved in the cell fusion induced by EGCg. Methods: We hypothesized that EGCg-induced oxidative stress might be involved in cell fusion, and used macrophage cell line RAW264.7 cells. We evaluated cell fusion activity after adding the antioxidants N-acetyl-l-cysteine (NAC) or catalase in addition to EGCg. The mRNA expressions of genes related to cell fusion and bone resorption were quantified by real-time PCR. Finally, we added hydrogen peroxide and examined its effects on cell fusion and TRAP activity. Results: EGCg-induced cell fusion was strongly inhibited by the addition of NAC in a dose-dependent manner (EGCg with 5 mM NAC; decreased to 1.5%; p < 0.05), while the inhibitory effect of catalase was limited (EGCg with 500 U/mL catalase; decreased to 27.7%; p < 0.05). DC-STAMP expression was significantly upregulated by EGCg compared with the untreated group, and the upregulation was significantly suppressed by 5 mM NAC. Conversely, Nfatc1 and TRAP expression were not upregulated by EGCg. These results suggest that EGCg induces DC-STAMP expression via reactive oxygen species production, which regulates cell fusion but does not affect the osteoclastic pathway. Although treatment with hydrogen peroxide promoted the formation of multinucleated cells, no increase in TRAP activity was observed, which was similar to EGCg treatment. Conclusions: This study suggests that the increased cell fusion by EGCg may be induced by oxidative stress due to reactive oxygen species production.
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spelling doaj.art-6b2f4619158c485e98d00fb6a2a11d5f2023-10-13T13:55:01ZengElsevierBiochemistry and Biophysics Reports2405-58082023-09-0135101536Green tea polyphenol EGCg induces cell fusion via reactive oxygen speciesKenji Kuriya0Shimon Itoh1Akihiro Isoda2Shoki Tanaka3Masahiro Nishio4Hayato Umekawa5Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, Japan; Corresponding author.Department of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, JapanDepartment of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, JapanDepartment of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, JapanDepartment of Life Sciences, Graduate School of Bioresources, Mie University, 1577 Kurimamachiya, Tsu, Mie, 514-8507, JapanMie Study Center, The Open University of Japan, 1234 Ishinden, Tsu, Mie, 514-0061, JapanBackground: Osteoclasts are multinucleated cells formed by macrophage cell fusion that are responsible for bone resorption. Previously, we found that treating osteoclastic progenitor cells with (−)-epigallocatechin gallate (EGCg) increased cell fusion. In this study, we aimed to identify factors involved in the cell fusion induced by EGCg. Methods: We hypothesized that EGCg-induced oxidative stress might be involved in cell fusion, and used macrophage cell line RAW264.7 cells. We evaluated cell fusion activity after adding the antioxidants N-acetyl-l-cysteine (NAC) or catalase in addition to EGCg. The mRNA expressions of genes related to cell fusion and bone resorption were quantified by real-time PCR. Finally, we added hydrogen peroxide and examined its effects on cell fusion and TRAP activity. Results: EGCg-induced cell fusion was strongly inhibited by the addition of NAC in a dose-dependent manner (EGCg with 5 mM NAC; decreased to 1.5%; p < 0.05), while the inhibitory effect of catalase was limited (EGCg with 500 U/mL catalase; decreased to 27.7%; p < 0.05). DC-STAMP expression was significantly upregulated by EGCg compared with the untreated group, and the upregulation was significantly suppressed by 5 mM NAC. Conversely, Nfatc1 and TRAP expression were not upregulated by EGCg. These results suggest that EGCg induces DC-STAMP expression via reactive oxygen species production, which regulates cell fusion but does not affect the osteoclastic pathway. Although treatment with hydrogen peroxide promoted the formation of multinucleated cells, no increase in TRAP activity was observed, which was similar to EGCg treatment. Conclusions: This study suggests that the increased cell fusion by EGCg may be induced by oxidative stress due to reactive oxygen species production.http://www.sciencedirect.com/science/article/pii/S2405580823001176Epigallocatechin gallateReactive oxygen speciesCell fusionDC-STAMPRAW264.7 cells
spellingShingle Kenji Kuriya
Shimon Itoh
Akihiro Isoda
Shoki Tanaka
Masahiro Nishio
Hayato Umekawa
Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
Biochemistry and Biophysics Reports
Epigallocatechin gallate
Reactive oxygen species
Cell fusion
DC-STAMP
RAW264.7 cells
title Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
title_full Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
title_fullStr Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
title_full_unstemmed Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
title_short Green tea polyphenol EGCg induces cell fusion via reactive oxygen species
title_sort green tea polyphenol egcg induces cell fusion via reactive oxygen species
topic Epigallocatechin gallate
Reactive oxygen species
Cell fusion
DC-STAMP
RAW264.7 cells
url http://www.sciencedirect.com/science/article/pii/S2405580823001176
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