title: Bisphosphonate-modified gold nanoparticles: a useful vehicle to study the treatment of osteonecrosis of the femoral head.
abstract: Legg-Calvé-Perthes disease (LCPD) is a juvenile form of osteonecrosis of the femoral head that presents in children aged 2-14 years. To date, there is no effective medical therapy for treating LCPD largely due to an inability to modulate the repair process, including the predominance of bone resorption. This investigation aims to evaluate the feasibility of using gold nanoparticles (GNPs) that are surface modified with a bisphosphonate compound for the treatment of osteonecrosis at the cellular level. Studies have found osteoclast-mediated resorption to be a process that contributes significantly to the pathogenesis of femoral head deformities arising from Perthes disease. Our in vitro model was designed to elucidate the effect of alendronate-(a bisphosphonate) modified GNPs, on osteoclastogenesis and osteoclast function. RAW 264.7 macrophage cells were cultured with recombinant mouse receptor activator of NF-κB ligand (RANKL), which stimulates osteoclastogenesis, and were then treated with alendronate-modified GNPs for 24, 48, and 72 h. Cell proliferation, osteoclast function, and osteoclast morphology were evaluated by trypan blue dye exclusion assay, tartrate-resistant acid phosphatase (TRAP) staining, and transmission electron microscopy (TEM) imaging. Comparative studies were performed with GNPs that were only stabilized with citrate ions and with alendronate alone. Neither osteoclastogenesis nor osteoclast function were adversely affected by the presence of the citrate-GNP. Alendronate-modified GNPs had an enhanced effect on inducing osteoclast apoptosis and impairing osteoclast function when compared to unbound alendronate populations.
authors.affiliation: Department of Chemical and Biomedical Engineering, University of South Florida, Tampa, FL 33620, USA.
authors.forename: Fedena
authors.initials: F
authors.lastname: Fanord
authors.forename: Korie
authors.initials: K
authors.lastname: Fairbairn
authors.forename: Harry
authors.initials: H
authors.lastname: Kim
authors.forename: Amanda
authors.initials: A
authors.lastname: Garces
authors.forename: Venkat
authors.initials: V
authors.lastname: Bhethanabotla
authors.forename: Vinay K
authors.initials: VK
authors.lastname: Gupta
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology*; D005271:Femur Head Necrosis / Q000628:therapy*; D006046:Gold / Q000494:pharmacology*; D007527:Isoenzymes / Q000378:metabolism; D053768:Metal Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D051379:Mice; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D010316:Particle Size; D017550:Spectroscopy, Fourier Transform Infrared; D000071681:Tartrate-Resistant Acid Phosphatase; D013997:Time Factors
chemical_list: D004164:Diphosphonates; D007527:Isoenzymes; D006046:Gold; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase