Issue 6, 2020

Carboxylated gold nanoparticles inhibit bone erosion by disturbing the acidification of an osteoclast absorption microenvironment

Abstract

Hyperactive osteoclasts (OCs) are a fundamental reason for excessive bone resorption and consequent osteoporosis that lead to one-third of the patients sustaining a fracture. OCs, with the help of acidifying vesicles containing vacuolar-type H+-ATPase (V-ATPase), transport cytoplasmic protons into a resorptive pit and create an acidic microenvironment where proteolytic enzymes degrade the bone matrix. Here, we report a previously undescribed application of gold nanoparticles (AuNPs) to inhibit excessive bone resorption by regulating the acidic microenvironment in which OCs resorb bone. Internalized AuNPs, with relatively abundant carboxyl groups, eventually accumulate in the membrane of the intracellular vesicles and interact with the V0 domain of V-ATPase, which prevents it from recruiting the V1 domain. This destroys the acid-secretion function of OCs. The therapeutic effect of AuNPs on bone resorption was assessed in an established lipopolysaccharide-induced bone erosion mouse model. Micro-computed tomography, histology, and tartrate-resistant acid phosphatase staining showed that AuNPs significantly reduced bone erosion. In summary, AuNPs are promising nano-functional materials for repairing bone defects by regulating OC acid secretion.

Graphical abstract: Carboxylated gold nanoparticles inhibit bone erosion by disturbing the acidification of an osteoclast absorption microenvironment

Supplementary files

Article information

Article type
Paper
Submitted
14 Nov 2019
Accepted
15 Jan 2020
First published
16 Jan 2020

Nanoscale, 2020,12, 3871-3878

Carboxylated gold nanoparticles inhibit bone erosion by disturbing the acidification of an osteoclast absorption microenvironment

X. Bai, Y. Gao, M. Zhang, Y. Chang, K. Chen, J. Li, J. Zhang, Y. Liang, J. Kong, Y. Wang, W. Liang, G. Xing, W. Li and G. Xing, Nanoscale, 2020, 12, 3871 DOI: 10.1039/C9NR09698A

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