Gene regulatory network analysis identifies MYL1, MDH2, GLS, and TRIM28 as the principal proteins in the response of mesenchymal stem cells to Mg 2+ ions.

Magnesium (Mg)-based implants have emerged as a promising alternative for orthopedic applications, owing to their bioactive properties and biodegradability. As the implants degrade, Mg2+ ions are released, influencing all surrounding cell types, especially mesenchymal stem cells (MSCs). MSCs are vital for bone tissue regeneration, therefore, it is essential to understand their molecular response to Mg2+ ions in order to maximize the potential of Mg-based biomaterials. In this study, we conducted a gene regulatory network (GRN) analysis to examine the molecular responses of MSCs to Mg2+ ions. We used time-series proteomics data collected at 11 time points across a 21-day period for the GRN construction. We studied the impact of Mg2+ ions on the resulting networks and identified the key proteins and protein interactions affected by the application of Mg2+ ions. Our analysis highlights MYL1, MDH2, GLS, and TRIM28 as the primary targets of Mg2+ ions in the response of MSCs during 1-21 days phase. Our results also identify MDH2-MYL1, MDH2-RPS26, TRIM28-AK1, TRIM28-SOD2, and GLS-AK1 as the critical protein relationships affected by Mg2+ ions. By offering a comprehensive understanding of the regulatory role of Mg2+ ions on MSCs, our study contributes valuable insights into the molecular response of MSCs to Mg-based materials, thereby facilitating the development of innovative therapeutic strategies for orthopedic applications.