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Sci Rep. 2019 Jan 30;9(1):933. doi: 10.1038/s41598-018-37091-8.

Regulation of osteogenesis and osteoclastogenesis by zoledronic acid loaded on biodegradable magnesium-strontium alloy.

Author information

1
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China.
2
Department of Orthopedics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China.
3
School of Mechanical Engineering, Dongguan University of Technology, Dongguan, 523808, China. wanpeng@dgut.edu.cn.
4
Institute of Metal Research, Chinese Academy of Sciences, Shenyang, 110016, China.
5
University of Chinese Academy of Sciences, Beijing, 100049, China.
6
Department of Orthopedics, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, China. luck_2001@126.com.
7
State Key Laboratory for Mechanical Behavior of Materials, Xi'an Jiaotong University, Xi'an, 710049, China. yonghan@mail.xjtu.edu.cn.

Abstract

Inhibiting osteoclasts and osteoclast precursors to reduce bone resorption is an important strategy to treat osteoclast-related diseases, such as peri-prosthetic osteolysis. In this study, our objective was to study the role of zoledronic acid (ZA), as a highly potent and nitrogen-containing bisphosphonate, in promoting osteogenesis and inhibiting osteoclastogenesis properties of magnesium (Mg)-based implants. ZA was chemically associated with calcium phosphate (CaP) deposited on magnesium-strontium (Mg-Sr) alloy, which was confirmed by the morphological observation, phase composition and drug releasing via SEM, XRD spectrum and High Performance Liquid Chromatography (HPLC), respectively. The in vitro performances indicated that ZA-CaP bilayer coating Mg-Sr alloy could enhance the proliferation and the osteogenic differentiation as well as the mineralization of pre-osteoblasts, however, induce the apoptosis and inhibit the osteoclast differentiation. We further investigated the possible molecular mechanisms by using Quantitative real-time PCR (qRT-PCR) and Western Blotting, and the results showed that ZA-CaP bilayer coating Mg-Sr alloy could regulate the osteogenesis and osteoclastogenesis through the Estrogen Receptor α (ERα) and NF-κB signaling pathway. Moreover, ZA-CaP bilayer coating Mg-Sr alloy could regulate the cross talk of osteoblast-osteoclast and increase the ratio of OPG: RANKL in the co-culture system through OPG/RANKL/RANK signaling pathway, which promoting the balance of bone remodeling process. Therefore, these promising results suggest the potential clinical applications of ZA pretreated Mg-Sr alloys for bone defect repairs and periprosthetical osteolysis due to the excessive differentitation and maturation of osteoclasts.

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