Bioactive Silica Nanoparticles Promote Osteoblast Differentiation through Stimulation of Autophagy and Direct Association with LC3 and p62
被引:165
作者:
Ha, Shin-Woo
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Emory Univ, Div Endocrinol, Dept Med, Atlanta, GA 30322 USAAtlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
Ha, Shin-Woo
[2
]
Weitzmann, M. Neale
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机构:
Atlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
Emory Univ, Div Endocrinol, Dept Med, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USAAtlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
Weitzmann, M. Neale
[1
,2
,3
]
Beck, George R., Jr.
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机构:
Atlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
Emory Univ, Div Endocrinol, Dept Med, Atlanta, GA 30322 USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USAAtlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
Beck, George R., Jr.
[1
,2
,3
]
机构:
[1] Atlanta Dept Vet Affairs Med Ctr, Decatur, GA 30033 USA
[2] Emory Univ, Div Endocrinol, Dept Med, Atlanta, GA 30322 USA
[3] Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA
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 LC3 beta-I to LC3 beta-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 LC3 beta and p62, two key proteins involved in autophagosome formation, with silica nanoparticles. Interestingly, NP1 specifically interacts with the active and autophagosome associated form of LC3 beta (LC3 beta-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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页码:5898 / 5910
页数:13
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[1]
Alcantar NA, 2000, J BIOMED MATER RES, V51, P343, DOI 10.1002/1097-4636(20000905)51:3<343::AID-JBM7>3.0.CO
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Beck, George R., Jr.
Ha, Shin-Woo
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Seoul Natl Univ, Dept Chem, Seoul, South KoreaEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Ha, Shin-Woo
Camalier, Corinne E.
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Camalier, Corinne E.
Yamaguchi, Masayoshi
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Yamaguchi, Masayoshi
Li, Yan
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Li, Yan
Lee, Jin-Kyu
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Seoul Natl Univ, Dept Chem, Seoul, South KoreaEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Lee, Jin-Kyu
Weitzmann, M. Neale
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA
Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
机构:
Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Beck, George R., Jr.
Ha, Shin-Woo
论文数: 0引用数: 0
h-index: 0
机构:
Seoul Natl Univ, Dept Chem, Seoul, South KoreaEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Ha, Shin-Woo
Camalier, Corinne E.
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Camalier, Corinne E.
Yamaguchi, Masayoshi
论文数: 0引用数: 0
h-index: 0
机构:
Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Yamaguchi, Masayoshi
Li, Yan
论文数: 0引用数: 0
h-index: 0
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Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Li, Yan
Lee, Jin-Kyu
论文数: 0引用数: 0
h-index: 0
机构:
Seoul Natl Univ, Dept Chem, Seoul, South KoreaEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Lee, Jin-Kyu
Weitzmann, M. Neale
论文数: 0引用数: 0
h-index: 0
机构:
Emory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA
Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA USA
Vet Affairs Med Ctr, Atlanta Dept, Decatur, GA 30033 USAEmory Univ, Sch Med, Div Endocrinol Metab & Lipids, Atlanta, GA USA