CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, 19B YuquanLu, Shijingshan District, Beijing, China.
CAS Key Lab for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, 19B YuquanLu, Shijingshan District, Beijing, China and Harbin First Hospital Affiliated to Harbin Institute of Technology, Beijing, China.
Nanoscale. 2020 Feb 14;12(6):3871-3878. doi: 10.1039/c9nr09698a. Epub 2020 Jan 30.
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.
破骨细胞（OCs）过度活跃是导致骨吸收过多和骨质疏松症的根本原因，这会导致三分之一的患者发生骨折。OCs 在含有液泡型 H+-ATP 酶（V-ATPase）的酸化小泡的帮助下，将细胞质中的质子转运到吸收陷窝中，并创造一个酸性微环境，其中蛋白水解酶降解骨基质。在这里，我们报告了金纳米颗粒（AuNPs）的一个以前未被描述的应用，通过调节破骨细胞吸收骨的酸性微环境来抑制过度骨吸收。具有相对丰富羧基的内化 AuNPs 最终会在细胞内囊泡的膜中积累，并与 V-ATPase 的 V0 结构域相互作用，从而阻止其募集 V1 结构域。这破坏了 OCs 的酸分泌功能。AuNPs 对骨吸收的治疗效果在已建立的脂多糖诱导的骨侵蚀小鼠模型中进行了评估。微计算机断层扫描、组织学和耐酒石酸酸性磷酸酶染色显示，AuNPs 可显著减少骨侵蚀。总之，AuNPs 是一种有前途的纳米功能材料，可通过调节 OC 酸分泌来修复骨缺损。
