Cargando…

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

BACKGROUND: 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 concent...

Descripción completa

Detalles Bibliográficos
Autores principales: Wang, Yabing, Xie, Jian, Ai, Zexin, Su, Jiansheng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769031/
https://www.ncbi.nlm.nih.gov/pubmed/31576127
http://dx.doi.org/10.2147/IJN.S213724
_version_ 1783455168672563200
author Wang, Yabing
Xie, Jian
Ai, Zexin
Su, Jiansheng
author_facet Wang, Yabing
Xie, Jian
Ai, Zexin
Su, Jiansheng
author_sort Wang, Yabing
collection PubMed
description BACKGROUND: 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.
format Online
Article
Text
id pubmed-6769031
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Dove
record_format MEDLINE/PubMed
spelling pubmed-67690312019-10-01 Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis Wang, Yabing Xie, Jian Ai, Zexin Su, Jiansheng Int J Nanomedicine Original Research BACKGROUND: 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. Dove 2019-09-26 /pmc/articles/PMC6769031/ /pubmed/31576127 http://dx.doi.org/10.2147/IJN.S213724 Text en © 2019 Wang et al. http://creativecommons.org/licenses/by-nc/3.0/ This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Wang, Yabing
Xie, Jian
Ai, Zexin
Su, Jiansheng
Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title 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_short Nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
title_sort nobiletin-loaded micelles reduce ovariectomy-induced bone loss by suppressing osteoclastogenesis
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6769031/
https://www.ncbi.nlm.nih.gov/pubmed/31576127
http://dx.doi.org/10.2147/IJN.S213724
work_keys_str_mv AT wangyabing nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis
AT xiejian nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis
AT aizexin nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis
AT sujiansheng nobiletinloadedmicellesreduceovariectomyinducedbonelossbysuppressingosteoclastogenesis