Neutralization of Intracellular pH Homeostasis to Inhibit Osteoclasts Based on a Spatiotemporally Selective Delivery System.

ABSTRACT: Osteoporosis is a global disease caused by abnormal overactivation of osteoclasts. The acidic environment in sealing zone of osteoclasts with H⁺ pumped from cytoplasm is critical to the maturation of osteoclasts. Therefore, reducing the intracellular H⁺ concentration can reduce the H⁺ secretion of osteoclasts from the source. In our study, we developed a novel nanovesicle which encapsulates Na₂HPO₄ with a liposome hybridizes with preosteoclast membrane (Na₂HPO₄@Lipo-pOCm). These nanovesicles release Na₂HPO₄ into the preosteoclast by targeting preosteoclasts and membrane fusion, reducing the intracellular H⁺ concentration, and achieve biological cascade regulation of osteoclasts through simple pH regulation. In vitro and in vivo experiments confirmed that these nanovesicles reduce mitochondrial membrane potential by decreasing intracellular H⁺ concentration, thereby reducing the ROS in osteoclasts as well as the expression of the upstream transcription factor FOXM1 of Acp5. In short, this nanovesicle can significantly inhibit the osteoclasts and ameliorate osteoporosis caused by OVX.

SUBMITTER: Tian H 

PROVIDER: S-EPMC10214447 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature