title: Bioactive silica-based nanoparticles stimulate bone-forming osteoblasts, suppress bone-resorbing osteoclasts, and enhance bone mineral density in vivo.
abstract: Bone is a dynamic tissue that undergoes renewal throughout life in a process whereby osteoclasts resorb worn bone and osteoblasts synthesize new bone. Imbalances in bone turnover lead to bone loss and development of osteoporosis and ultimately fracture, a debilitating condition with high morbidity and mortality. Silica is a ubiquitous biocontaminant that is considered to have high biocompatibility. The authors report that silica nanoparticles (NPs) mediate potent inhibitory effects on osteoclasts and stimulatory effects on osteoblasts in vitro. The mechanism of bioactivity is a consequence of an intrinsic capacity to antagonize activation of NF-κB, a signal transduction pathway required for osteoclastic bone resorption but inhibitory to osteoblastic bone formation. We further demonstrate that silica NPs promote a significant enhancement of bone mineral density (BMD) in mice in vivo, providing a proof of principle for the potential application of silica NPs as a pharmacological agent to enhance BMD and protect against bone fracture.
authors.affiliation: The Division of Endocrinology, Metabolism and Lipids, Emory University School of Medicine, Atlanta, Georgia 30322-0001, USA.
authors.forename: George R
authors.initials: GR
authors.lastname: Beck
authors.forename: Shin-Woo
authors.initials: SW
authors.lastname: Ha
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Camalier
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Yamaguchi
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Lee
authors.forename: M Neale
authors.initials: MN
authors.lastname: Weitzmann
mesh_terms: D016475:3T3 Cells; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D001862:Bone Resorption / Q000473:pathology / Q000503:physiopathology* / Q000517:prevention & control*; D018786:Bone Substitutes / Q000008:administration & dosage; D005260:Female; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D053769:Nanocapsules / Q000008:administration & dosage*; D010006:Osteoblasts / Q000187:drug effects* / Q000473:pathology; D010010:Osteoclasts / Q000187:drug effects* / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D012822:Silicon Dioxide / Q000008:administration & dosage*
chemical_list: D018786:Bone Substitutes; D053769:Nanocapsules; D012822:Silicon Dioxide
references.citation: Mol Cell Biol. 2000 Dec;20(23):8783-92
references.pmid: 11073979
references.citation: J Bone Miner Res. 2007 May;22(5):646-55
references.pmid: 17266397
references.citation: Mol Cell Biochem. 2011 Sep;355(1-2):179-86
references.pmid: 21533765
references.citation: J Biomed Mater Res B Appl Biomater. 2009 Jul;90(1):123-30
references.pmid: 19194862
references.citation: J Nutr Health Aging. 2007 Mar-Apr;11(2):99-110
references.pmid: 17435952
references.citation: Cell. 2002 Jan 11;108(1):17-29
references.pmid: 11792318
references.citation: Gene. 2003 Dec 4;321:1-15
references.pmid: 14636987
references.citation: Cancer Prev Res (Phila). 2010 Mar;3(3):359-70
references.pmid: 20145188
references.citation: J Bone Miner Res. 1992 Nov;7(11):1281-9
references.pmid: 1334616
references.citation: Ann N Y Acad Sci. 2010 Mar;1192:367-75
references.pmid: 20392262
references.citation: Bone. 1999 Jul;25(1):137-9
references.pmid: 10423039
references.citation: J Nutr Health Aging. 2007 Mar-Apr;11(2):94-7
references.pmid: 17435951
references.citation: Cell. 1997 May 30;89(5):747-54
references.pmid: 9182762
references.citation: J Biomed Mater Res. 1999 Mar 15;44(4):422-8
references.pmid: 10397946
references.citation: Small. 2006 Feb;2(2):209-15
references.pmid: 17193022
references.citation: Free Radic Biol Med. 2008 Apr 1;44(7):1246-58
references.pmid: 18226603
references.citation: J Bone Miner Res. 2003 Feb;18(2):260-9
references.pmid: 12568403
references.citation: Nature. 1972 Oct 6;239(5371):333-4
references.pmid: 12635226
references.citation: Toxicol Lett. 2009 Jan 10;184(1):18-25
references.pmid: 19022359
references.citation: J Clin Invest. 2006 May;116(5):1186-94
references.pmid: 16670759
references.citation: Mol Med Rep. 2009 Jul-Aug;2(4):641-4
references.pmid: 21475879
references.citation: Int J Mol Med. 2011 Jan;27(1):3-14
references.pmid: 21072493
references.citation: Int J Mol Med. 2009 Feb;23(2):297-301
references.pmid: 19148557
references.citation: J Mater Sci Mater Med. 2011 Jun;22(6):1489-99
references.pmid: 21567286
references.citation: Int J Mol Med. 2011 Oct;28(4):521-5
references.pmid: 21769418
references.citation: J Biol Chem. 2007 Sep 14;282(37):27285-27297
references.pmid: 17623659
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 3;107(31):13848-53
references.pmid: 20643942
references.citation: Nano Lett. 2009 Jul;9(7):2763-8
references.pmid: 19537737
references.citation: Ann Periodontol. 2001 Dec;6(1):197-208
references.pmid: 11887465
references.citation: FASEB J. 2005 Dec;19(14):2014-6
references.pmid: 16230334
references.citation: J Biol Chem. 2002 Jan 25;277(4):2695-701
references.pmid: 11723115
references.citation: J Vet Sci. 2006 Dec;7(4):321-6
references.pmid: 17106221
references.citation: Proc Natl Acad Sci U S A. 2007 Sep 18;104(38):15087-92
references.pmid: 17848519
references.citation: Chem Commun (Camb). 2009 May 28;(20):2881-3
references.pmid: 19436897
references.citation: Proc Natl Acad Sci U S A. 2003 Jan 7;100(1):125-30
references.pmid: 12490655
references.citation: Int J Mol Med. 2009 Nov;24(5):671-5
references.pmid: 19787201
references.citation: Science. 2000 Sep 1;289(5484):1504-8
references.pmid: 10968780
references.citation: Langmuir. 2008 Jul 15;24(14):7354-64
references.pmid: 18553993
references.citation: Nano Lett. 2010 Jan;10(1):59-63
references.pmid: 19994869
references.citation: J Exp Med. 2003 Sep 1;198(5):771-81
references.pmid: 12939342
references.citation: Endocr Rev. 2002 Jun;23(3):279-302
references.pmid: 12050121
references.citation: J Cell Biol. 1983 Jan;96(1):191-8
references.pmid: 6826647
references.citation: Toxicol Lett. 2009 Sep 28;189(3):177-83
references.pmid: 19397964
references.citation: J Bone Miner Res. 1999 Jun;14(6):893-903
references.pmid: 10352097
references.citation: J Cell Biochem. 1998 Feb 1;68(2):269-80
references.pmid: 9443082