Toxoplasma gondii excretory/secretory proteins promotes osteogenic differentiation of bone marrow mesenchymal stem cells via aerobic glycolysis mediated by Wnt/β‑catenin signaling pathway

Toxoplasma gondii excretory/secretory proteins (TgESPs) are a group of proteins secreted by the Parasite and have an important role in the interaction between the host and Toxoplasma gondii (T. gondii). They can participate in various biological processes in different cells and regulate cellular energy metabolism. However, the effect of TgESPs on energy metabolism and osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) has remained elusive. In the present study, TgESPs were extracted from the T. gondii RH strain and used to treat BMSCs to observe the effect of TgESPs on energy metabolism and osteogenic differentiation of BMSCs and to explore the molecular mechanisms involved. The osteogenic differentiation and energy metabolism of BMSCs were evaluated using Alizarin Red S staining, qRT-PCR, western blot, immunofluorescence and Seahorse extracellular flux assays. The results indicated that TgESPs activated the Wnt/β‑catenin signaling pathway to enhance glycolysis and lactate production in BMSCs, and promoted cell mineralization and expression of osteogenic markers. In conclusion, the present study uncovered the potential mechanism by which TgESPs regulate BMSCs, which will provide a theoretical reference for the study of the function of TgESPs in the future.

Toxoplasma gondii excretory/secretory proteins; Wnt/β‑catenin signaling pathway; aerobic glycolysis; bone marrow mesenchymal stem cells; osteogenic differentiation.