Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62

[Image: see text] We recently identified an engineered bioactive silica-based nanoparticle formulation (designated herein as NP1) that stimulates in vitro differentiation and mineralization of osteoblasts, the cells responsible for bone formation, and increases bone mineral density in young mice in...

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Autores principales: Ha, Shin-Woo, Weitzmann, M. Neale, Beck, George R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076025/
https://www.ncbi.nlm.nih.gov/pubmed/24806912
http://dx.doi.org/10.1021/nn5009879
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author Ha, Shin-Woo
Weitzmann, M. Neale
Beck, George R.
author_facet Ha, Shin-Woo
Weitzmann, M. Neale
Beck, George R.
author_sort Ha, Shin-Woo
collection PubMed
description [Image: see text] We recently identified an engineered bioactive silica-based nanoparticle formulation (designated herein as NP1) that stimulates in vitro differentiation and mineralization of osteoblasts, the cells responsible for bone formation, and increases bone mineral density in young mice in vivo. The results demonstrate that these nanoparticles have intrinsic biological activity; however, the intracellular fate and a complete understanding of the mechanism(s) involved remains to be elucidated. Here we investigated the cellular mechanism(s) by which NP1 stimulates differentiation and mineralization of osteoblasts. We show that NP1 enters the cells through a caveolae-mediated endocytosis followed by stimulation of the mitogen activated protein kinase ERK1/2 (p44/p42). Our findings further revealed that NP1 stimulates autophagy including the processing of LC3β-I to LC3β-II, a key protein involved in autophagosome formation, which is dependent on ERK1/2 signaling. Using a variant of NP1 with cobalt ferrite magnetic metal core (NP1-MNP) to pull down associated proteins, we found direct binding of LC3β and p62, two key proteins involved in autophagosome formation, with silica nanoparticles. Interestingly, NP1 specifically interacts with the active and autophagosome associated form of LC3β (LC3β-II). Taken together, the stimulation of autophagy and associated signaling suggests a cellular mechanism for the stimulatory effects of silica nanoparticles on osteoblast differentiation and mineralization.
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spelling pubmed-40760252015-05-07 Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62 Ha, Shin-Woo Weitzmann, M. Neale Beck, George R. ACS Nano [Image: see text] We recently identified an engineered bioactive silica-based nanoparticle formulation (designated herein as NP1) that stimulates in vitro differentiation and mineralization of osteoblasts, the cells responsible for bone formation, and increases bone mineral density in young mice in vivo. The results demonstrate that these nanoparticles have intrinsic biological activity; however, the intracellular fate and a complete understanding of the mechanism(s) involved remains to be elucidated. Here we investigated the cellular mechanism(s) by which NP1 stimulates differentiation and mineralization of osteoblasts. We show that NP1 enters the cells through a caveolae-mediated endocytosis followed by stimulation of the mitogen activated protein kinase ERK1/2 (p44/p42). Our findings further revealed that NP1 stimulates autophagy including the processing of LC3β-I to LC3β-II, a key protein involved in autophagosome formation, which is dependent on ERK1/2 signaling. Using a variant of NP1 with cobalt ferrite magnetic metal core (NP1-MNP) to pull down associated proteins, we found direct binding of LC3β and p62, two key proteins involved in autophagosome formation, with silica nanoparticles. Interestingly, NP1 specifically interacts with the active and autophagosome associated form of LC3β (LC3β-II). Taken together, the stimulation of autophagy and associated signaling suggests a cellular mechanism for the stimulatory effects of silica nanoparticles on osteoblast differentiation and mineralization. American Chemical Society 2014-05-07 2014-06-24 /pmc/articles/PMC4076025/ /pubmed/24806912 http://dx.doi.org/10.1021/nn5009879 Text en Copyright © 2014 American Chemical Society Terms of Use (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html)
spellingShingle Ha, Shin-Woo
Weitzmann, M. Neale
Beck, George R.
Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title_full Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title_fullStr Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title_full_unstemmed Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title_short Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
title_sort bioactive silica nanoparticles promote osteoblast differentiation through stimulation of autophagy and direct association with lc3 and p62
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4076025/
https://www.ncbi.nlm.nih.gov/pubmed/24806912
http://dx.doi.org/10.1021/nn5009879
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