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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 <jats:italic>in vitro<\/jats:italic> 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 \u03b1 (ER\u03b1) and NF-\u03baB 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.<\/jats:p>","DOI":"10.1038\/s41598-018-37091-8","type":"journal-article","created":{"date-parts":[[2019,1,30]],"date-time":"2019-01-30T11:04:42Z","timestamp":1548846282000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Regulation of osteogenesis and osteoclastogenesis by zoledronic acid loaded on biodegradable magnesium-strontium alloy"],"prefix":"10.1038","volume":"9","author":[{"given":"Mei","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peng","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weidan","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2019,1,30]]},"reference":[{"key":"37091_CR1","doi-asserted-by":"publisher","first-page":"2442","DOI":"10.1016\/j.actbio.2012.04.012","volume":"8","author":"H Hornberger","year":"2012","unstructured":"Hornberger, H., Virtanen, S. & Boccaccini, A. 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