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表没食子儿茶素没食子酸酯功能化的金纳米粒子在体外和体内的抗破骨原性作用
Authors Zhu S, Zhu L, Yu J, Wang Y, Peng B
Received 9 February 2019
Accepted for publication 3 May 2019
Published 8 July 2019 Volume 2019:14 Pages 5017—5032
DOI https://doi.org/10.2147/IJN.S204628
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Mian Wang
Background: Epigallocatechin gallate (EGCG), the major anti-inflammatory compound in green tea, has been shown to suppress osteoclast (OC) differentiation. However, the low aqueous solubility of EGCG always leads to poor bioavailability, adverse effects, and several drawbacks for clinical applications.
Purpose: In this study, we synthesized EGCG-capped gold nanoparticles (EGCG-GNPs) to solve the drawbacks for clinical uses of EGCG in bone destruction disorders by direct reduction of HAuCl4 in EGCG aqueous solution.
Methods and Results: The obtained EGCG-GNPs were negatively charged and spherical. Theoretical calculation results suggested that EGCG was released from GNPs in an acidic environment. Cellular uptake study showed an obviously large amount of intracellular EGCG-GNPs without cytotoxicity. EGCG-GNPs exhibited better effects in reducing intracellular reactive oxygen species levels than free EGCG. A more dramatic anti-osteoclastogenic effect induced by EGCG-GNPs than free EGCG was observed in lipopolysaccharide (LPS)-stimulated bone marrow macrophages, including decreased formation of TRAP-positive multinuclear cells and actin rings. Meanwhile, EGCG-GNPs not only suppressed the mRNA expression of genetic markers of OC differentiation but also inhibited MAPK signaling pathways. Furthermore, we confirmed that EGCG-GNPs greatly reversed bone resorption in the LPS-induced calvarial bone erosion model in vivo, which was more effective than applying free EGCG, specifically in inhibiting the number of OCs, improving bone density, and preventing bone loss.
Conclusion: EGCG-GNPs showed better anti-osteoclastogenic effect than free EGCG in vitro and in vivo, indicating their potential in anti-bone resorption treatment strategy.
Keywords: epigallocatechin gallate, gold nanoparticles, bone marrow macrophages, lipopolysaccharide, calvarial bone