Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis

Abstract

The role of the calcifying nanoparticles (CNPs) in the calcification process of the outer cyst wall in hepatic cystic echinococcosis (HCE) remains unknown. CNPs were isolated from the tissues of the patients with HCE. Western blotting, alkaline phosphatase staining, and alizarin staining were performed to detect the cellular calcium ion deposition induced by the CNPs. CCK-8 and flow cytometry assays were conducted to determine the effect of CNPs on the apoptosis of mesenchymal stem cells (MSCs). Western blot experiments were performed to examine the expression levels of apoptosis-related factors and TGF-β1/Smad signaling pathway constituents. Treatment with CNPs induced the differentiation of MSCs. Calcium-related proteins, including OPN, BMP-2, and RUNX2, were upregulated after the CNP treatment. Similarly, CNP exposure increased the cellular calcium ion deposition in MSCs. In addition, the expression of Bax and Caspase-8 was elevated by the CNPs in MSCs. Treatment with CNPs promoted MSC apoptosis and inhibited the MSC growth. The TGF-β1/Smad signaling pathway was also activated after the CNP treatment. This study indicated that CNPs may play a critical role in initiating calcification of the outer cyst wall of HCE and promote the decay of echinococcosis, providing a new strategy for the treatment of hepatic echinococcosis.

Keywords

• calcifying nanoparticles
• mesenchymal stem cells
• hepatic echinococcosis
• calcification
• apoptosis