TRPM7 Mediates Mechanosensitivity in Adult Rat Odontoblasts

Abstract

Odontoblasts, with their strategic arrangement along the outermost compartment of the dentin-pulp complex, have been suggested to have sensory function. In addition to their primary role in dentin formation, growing evidence shows that odontoblasts are capable of sensing mechanical stimulation. Previously, we found that most odontoblasts express TRPM7, the nonselective mechanosensitive ion channel reported to be critical in Mg2+ homeostasis and dentin mineralization. In line with this finding, we sought to elucidate the functional expression of TRPM7 in odontoblasts by pharmacological approaches and mechanical stimulation. Naltriben, a TRPM7-specific agonist, induced calcium transient in the majority of odontoblasts, which was blocked by TRPM7 blockers such as extracellular Mg2+ and FTY720 in a dose-dependent manner. Mechanical stretch of the odontoblastic membrane with hypotonic solution also induced calcium transient, which was blocked by Gd3+, a nonselective mechanosensitive channel blocker. Calcium transient induced by hypotonic solution was also blocked by high extracellular Mg2+ or FTY720. When TRPM7-mediated calcium transients in odontoblasts were analyzed on the subcellular level, remarkably larger transients were detected in the distal odontoblastic process compared with the soma, which was further verified with comparable immunocytochemical analysis. Our results demonstrate that TRPM7 in odontoblasts can serve as a mechanical sensor, with its distribution to facilitate intracellular Ca2+ signaling in the odontoblastic process. These findings suggest TRPM7 as a mechanical transducer in odontoblasts to mediate intracellular calcium dynamics under diverse pathophysiological conditions of the dentin.