Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo

Shenting Zhu,* Lingxin Zhu,* Jingjing Yu, Yanqing Wang, Bin PengState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic...

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Autores principales: Zhu S, Zhu L, Yu J, Wang Y, Peng B
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Publicado: Dove Medical Press 2019
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spelling oai:doaj.org-article:d796d09e7754462f8be1b6de9fc0a4ec2021-12-02T09:27:13ZAnti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo1178-2013https://doaj.org/article/d796d09e7754462f8be1b6de9fc0a4ec2019-07-01T00:00:00Zhttps://www.dovepress.com/anti-osteoclastogenic-effect-of-epigallocatechin-gallate-functionalize-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Shenting Zhu,* Lingxin Zhu,* Jingjing Yu, Yanqing Wang, Bin PengState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workBackground: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications.Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl4 in EGCG aqueous solution.Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss.Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.Keywords: epigallocatechin gallate, gold nanoparticles, bone marrow macrophages, lipopolysaccharide, calvarial boneZhu SZhu LYu JWang YPeng BDove Medical PressarticleEpigallocatechin gallateGold nanoparticlesBone marrow macrophagesLipopolysaccharideCalvarial boneMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 5017-5032 (2019)
institution DOAJ
collection DOAJ
language EN
topic Epigallocatechin gallate
Gold nanoparticles
Bone marrow macrophages
Lipopolysaccharide
Calvarial bone
Medicine (General)
R5-920
spellingShingle Epigallocatechin gallate
Gold nanoparticles
Bone marrow macrophages
Lipopolysaccharide
Calvarial bone
Medicine (General)
R5-920
Zhu S
Zhu L
Yu J
Wang Y
Peng B
Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
description Shenting Zhu,* Lingxin Zhu,* Jingjing Yu, Yanqing Wang, Bin PengState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, People’s Republic of China*These authors contributed equally to this workBackground: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications.Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl4 in EGCG aqueous solution.Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss.Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.Keywords: epigallocatechin gallate, gold nanoparticles, bone marrow macrophages, lipopolysaccharide, calvarial bone
format article
author Zhu S
Zhu L
Yu J
Wang Y
Peng B
author_facet Zhu S
Zhu L
Yu J
Wang Y
Peng B
author_sort Zhu S
title Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
title_short Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
title_full Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
title_fullStr Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
title_full_unstemmed Anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
title_sort anti-osteoclastogenic effect of epigallocatechin gallate-functionalized gold nanoparticles in vitro and in vivo
publisher Dove Medical Press
publishDate 2019
url https://doaj.org/article/d796d09e7754462f8be1b6de9fc0a4ec
work_keys_str_mv AT zhus antiosteoclastogeniceffectofepigallocatechingallatefunctionalizedgoldnanoparticlesinvitroandinvivo
AT zhul antiosteoclastogeniceffectofepigallocatechingallatefunctionalizedgoldnanoparticlesinvitroandinvivo
AT yuj antiosteoclastogeniceffectofepigallocatechingallatefunctionalizedgoldnanoparticlesinvitroandinvivo
AT wangy antiosteoclastogeniceffectofepigallocatechingallatefunctionalizedgoldnanoparticlesinvitroandinvivo
AT pengb antiosteoclastogeniceffectofepigallocatechingallatefunctionalizedgoldnanoparticlesinvitroandinvivo
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