Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis

Yabing Wang,1 Jian Xie,1 Zexin Ai,2 Jiansheng Su1 1Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of China; 2Department of Oral and Max...

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Autores principales:	Wang Y, Xie J, Ai Z, Su J
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	Nobiletin micelles TRAP ovariectomized (OVX) mice Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e2698c212b75465789f0b1be9fed7a41
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spelling	oai:doaj.org-article:e2698c212b75465789f0b1be9fed7a412021-12-02T11:05:12ZNobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis1178-2013https://doaj.org/article/e2698c212b75465789f0b1be9fed7a412019-09-01T00:00:00Zhttps://www.dovepress.com/nobiletin-loaded-micelles-reduce-ovariectomy-induced-bone-loss-by-supp-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Yabing Wang,1 Jian Xie,1 Zexin Ai,2 Jiansheng Su1 1Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of ChinaCorrespondence: Jiansheng SuDepartment of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of ChinaTel +86 215 672 2215Fax +86 216 652 4025Email sjs@tongji.edu.cnBackground: Nobiletin (NOB), a polymethoxy flavonoid, possesses anti-cancer and anti-inflammatory activities, has been reported that it played role in anti-osteoporosis treatment. However, previous research did not focus on practical use due to lack of hydrophilicity and cytotoxicity at high concentrations. The aim of this study was to develop a therapeutic formulation for osteoporosis based on the utilization of NOB.Methods: In this study, NOB-loaded poly(ethylene glycol)-block-poly(e-caprolactone) (NOB-PEG-PCL) was prepared by dialysis method. The effects on osteoclasts and anti-osteoporosis functions were investigated in a RANKL-induced cell model and ovariectomized (OVX) mice.Results: Dynamic light scattering and transmission electron microscopy examination results revealed that the NOB-PEG-PCL had a round shape, with a mean diameter around 124 nm. The encapsulation efficiency and drug loading were 76.34±3.25% and 7.60±0.48%, respectively. The in vitro release of NOB from NOB-PEG-PCL showed a remarkably sustained releasing characteristic and could be retained at least 48 hrs in pH 7.4 PBS. Anti-osteoclasts effects demonstrated that the NOB-PEG-PCL significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells stimulated by RANKL. Furthermore, the NOB-PEG-PCL did not produce cytotoxicity on bone marrow-derived macrophages (BMMs). The mRNA expressions of genetic markers of osteoclasts including TRAP and cathepsin K were signiﬁcantly decreased in the presence of NOB-PEG-PCL. In addition, the NOB-PEG-PCL inhibited OC differentiation of BMMs through RANKL-induced MAPK signal pathway. After administration of the NOB-PEG-PCL, NOB-PEG-PCL prevented bone loss and improved bone density in OVX mice. These findings suggest that NOB-PEG-PCL might have great potential in the treatment of osteoporosis.Conclusion: The results suggested that NOB-PEG-PCL micelles could effectively prevent NOB fast release from micelles and extend circulation time. The NOB-PEG-PCL delivery system may be a promising way to prevent and treat osteoporosis.Keywords: nobiletin, micelles, TRAP, ovariectomized (OVX) miceWang YXie JAi ZSu JDove Medical PressarticleNobiletinmicellesTRAPovariectomized (OVX) miceMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 7839-7849 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Nobiletin micelles TRAP ovariectomized (OVX) mice Medicine (General) R5-920
spellingShingle	Nobiletin micelles TRAP ovariectomized (OVX) mice Medicine (General) R5-920 Wang Y Xie J Ai Z Su J Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
description	Yabing Wang,1 Jian Xie,1 Zexin Ai,2 Jiansheng Su1 1Department of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of ChinaCorrespondence: Jiansheng SuDepartment of Prosthodontics, School & Hospital of Stomatology, Tongji University, Shanghai Engineering Research Center of Tooth Restoration and Regeneration, Shanghai 200072, People’s Republic of ChinaTel +86 215 672 2215Fax +86 216 652 4025Email sjs@tongji.edu.cnBackground: Nobiletin (NOB), a polymethoxy flavonoid, possesses anti-cancer and anti-inflammatory activities, has been reported that it played role in anti-osteoporosis treatment. However, previous research did not focus on practical use due to lack of hydrophilicity and cytotoxicity at high concentrations. The aim of this study was to develop a therapeutic formulation for osteoporosis based on the utilization of NOB.Methods: In this study, NOB-loaded poly(ethylene glycol)-block-poly(e-caprolactone) (NOB-PEG-PCL) was prepared by dialysis method. The effects on osteoclasts and anti-osteoporosis functions were investigated in a RANKL-induced cell model and ovariectomized (OVX) mice.Results: Dynamic light scattering and transmission electron microscopy examination results revealed that the NOB-PEG-PCL had a round shape, with a mean diameter around 124 nm. The encapsulation efficiency and drug loading were 76.34±3.25% and 7.60±0.48%, respectively. The in vitro release of NOB from NOB-PEG-PCL showed a remarkably sustained releasing characteristic and could be retained at least 48 hrs in pH 7.4 PBS. Anti-osteoclasts effects demonstrated that the NOB-PEG-PCL significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells stimulated by RANKL. Furthermore, the NOB-PEG-PCL did not produce cytotoxicity on bone marrow-derived macrophages (BMMs). The mRNA expressions of genetic markers of osteoclasts including TRAP and cathepsin K were signiﬁcantly decreased in the presence of NOB-PEG-PCL. In addition, the NOB-PEG-PCL inhibited OC differentiation of BMMs through RANKL-induced MAPK signal pathway. After administration of the NOB-PEG-PCL, NOB-PEG-PCL prevented bone loss and improved bone density in OVX mice. These findings suggest that NOB-PEG-PCL might have great potential in the treatment of osteoporosis.Conclusion: The results suggested that NOB-PEG-PCL micelles could effectively prevent NOB fast release from micelles and extend circulation time. The NOB-PEG-PCL delivery system may be a promising way to prevent and treat osteoporosis.Keywords: nobiletin, micelles, TRAP, ovariectomized (OVX) mice
format	article
author	Wang Y Xie J Ai Z Su J
author_facet	Wang Y Xie J Ai Z Su J
author_sort	Wang Y
title	Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_short	Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_full	Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_fullStr	Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_full_unstemmed	Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_sort	nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/e2698c212b75465789f0b1be9fed7a41
work_keys_str_mv	AT wangy nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis AT xiej nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis AT aiz nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis AT suj nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis
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Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis

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