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.
Graphical Abstract
Activation of the NF-κB signal transduction pathway is central to the formation and activity of bone-degrading osteoclasts but is potently inhibitory to the differentiation and activity of bone building osteoblasts. Silica nanoparticles suppress osteoclasts and stimulate osteoblasts in vitro by antagonizing activation of NF-κB. When injected into mice in vivo, silica nanoparticles promote the accretion of bone mineral density. Consequently silica nanoparticles may have clinical potential as novel anti-osteoporotic pharmaceuticals.
Key words: Bone, Nanoparticle, Osteoclast, Osteoblast, Silica
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This study was supported by a grant from NIAMS (AR056090) and by a Georgia Research Alliance grant (GRA.VL12.C2) to M.N. Weitzmann and G.R. Beck. M.N. Weitzmann is also supported in part by funding from the Biomedical Laboratory Research & Development Service of the VA Office of Research and Development (5I01BX000105) and by grants AR059364 and AR053607 from NIAMS and AG040013 from NIA. G.R. Beck is also supported in part by NCI grants (CA136059 and CA136716). J-K. Lee expresses his thanks for a fellowship from the SBS Foundation in Korea to initiate this research collaboration.
PII: S1549-9634(11)00523-5
doi:10.1016/j.nano.2011.11.003
Published by Elsevier Inc.
