The Critical Role of MTA in Enhancing Immune Cell Migration

Objectives: Mineral trioxide aggregate (MTA) has been introduced as a choice material for regenerative dentistry. To date, the diverse biological activities of MTA, including its anti-inflammatory effects, have been extensively discussed. In this study, we report the role of MTA in enhancing both chemotactic and chemokinetic immune cell migration through distinct signaling pathways.
Methods: We revealed that MTA enhanced the motile abilities of immune cells through diverse approaches for documenting migration such as the transwell migration assay, 2D migration tracking, and recently developed optogenetic approaches, live cell imaging and photoactivation. The involvement of calcium-sensing receptor was identified by reverse transcriptase-polymerase chain reaction (RT-PCR) and Immunofluorescence. The kinetic activation of Cdc42 and myosin light chains phosphorylation in response to MTA was detected through pull-down assays and immunoblotting.
Results: By using versatile live imaging techniques, we demonstrated that MTA-mediated CaSR activation induced diverse downstream pathways to govern cell migratory capacity. In this context, Cdc42 generates cytoskeleton-driven cellular protrusions to steer directional cell migration (chemotaxis) through the phosphatidylinositol 3 kinase pathway. Whereas, Ca²⁺-calmodulin dependent myosin light chain kinase (MLCK) induces cell contractility that plays an important role in speeding up the average migration speed (chemokinesis). Moreover, perturbation of MLCK induced myosin light chain phosphorylation process completely turned off the cell motility, and also the chemotactic response, indicating that MLCK-induced cell contractility plays a fundamental role-giving a starting signal-in immune cell migration.
Conclusions: Our findings illuminate an unrecognized role for MTA and the related CaSR signaling network in immune cell migration, providing evidence that can drive the development of novel approaches to immunological therapy.