title: Inhibition of osteoclast differentiation by gold nanoparticles functionalized with cyclodextrin curcumin complexes.
abstract: Gold nanoparticles (GNPs) have been previously reported to inhibit osteoclast (OC) formation. However, previous research only confirmed the osteoclastogenesis inhibitory effect under in vitro conditions. The aim of this study was to develop a therapeutic agent for osteoporosis based on the utilization of GNPs and confirm their effect both in vitro and in vivo. We prepared β-cyclodextrin (CD) conjugated GNPs (CGNPs), which can form inclusion complexes with curcumin (CUR-CGNPs), and used these to investigate their inhibitory effects on receptor activator of nuclear factor-κb ligand (RANKL)-induced osteoclastogenesis in bone marrow-derived macrophages (BMMs). The CUR-CGNPs significantly inhibited the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells in BMMs without inducing cytotoxicity. The mRNA expressions of genetic markers of OC differentiation including c-Fos, nuclear factor of activated T cells 1 (NFATc1), TRAP, and osteoclast associated receptor (OSCAR) were significantly decreased in the presence of CUR-CGNPs. In addition, the CUR-CGNPs inhibited OC differentiation of BMMs through suppression of the RANKL-induced signaling pathway. Additionally, CUR-CGNPs caused a decrease in RANKL-induced actin ring formation, which is an essential morphological characteristic of OC formation allowing them to carry out bone resorption activity. Furthermore, the in vivo results of an ovariectomy (OVX)-induced osteoporosis model showed that CUR-CGNPs significantly improved bone density and prevented bone loss. Therefore, CUR-CGNPs may prove to be useful as therapeutic agents for preventing and treating osteoporosis.
authors.affiliation: Department of Maxillofacial Biomedical Engineering and Institute of Oral Biology, School of Dentistry, ‡Department of Conservative Dentistry, School of Dentistry, §Department of Dental Education, School of Dentistry, and ⊥Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth and Periodontal Regeneration (MRC), Kyung Hee University , Seoul 130-701, Republic of Korea.
authors.forename: Dong Nyoung
authors.initials: DN
authors.lastname: Heo
authors.forename: Wan-Kyu
authors.initials: WK
authors.lastname: Ko
authors.forename: Ho-Jin
authors.initials: HJ
authors.lastname: Moon
authors.forename: Han-Jun
authors.initials: HJ
authors.lastname: Kim
authors.forename: Sang Jin
authors.initials: SJ
authors.lastname: Lee
authors.forename: Jung Bok
authors.initials: JB
authors.lastname: Lee
authors.forename: Min Soo
authors.initials: MS
authors.lastname: Bae
authors.forename: Jin-Kyu
authors.initials: JK
authors.lastname: Yi
authors.forename: Yu-Shik
authors.initials: YS
authors.lastname: Hwang
authors.forename: Jae Beum
authors.initials: JB
authors.lastname: Bang
authors.forename: Eun-Cheol
authors.initials: EC
authors.lastname: Kim
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Do
authors.forename: Il Keun
authors.initials: IK
authors.lastname: Kwon
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry* / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006046:Gold / Q000737:chemistry*; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D000199:Actins; D053245:RANK Ligand; D047392:beta-Cyclodextrins; D006046:Gold; D003474:Curcumin; C031215:betadex
keywords: curcumin; gold nanoparticles; osteoclast differentiation; osteoporosis RANK signaling