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

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...

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Bibliographic Details
Published in:Nanoscale 2020-02, Vol.12 (6), p.3871-3878
Main Authors: Bai, Xue, Gao, Yuan, Zhang, Mingyi, Chang, Ya-nan, Chen, Kui, Li, Juan, Zhang, Jiaxin, Liang, Yuelan, Kong, Jianglong, Wang, Yujiao, Liang, Wei, Xing, Gengyan, Li, Wei, Xing, Gengmei
Format: Article
Language:English
Subjects:
Acid phosphatase
Acid resistance
Acidification
Biomedical materials
Computed tomography
Domains
Functional materials
Gold
Histology
Mouse devices
Nanoparticles
Osteoporosis
Vesicles
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Summary: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. Schematic of the mechanism by which a gold nanoparticle inhibits bone erosion.
ISSN:2040-3364
2040-3372
DOI:10.1039/c9nr09698a