Masticatory Stress Maintains Mucosal Homeostasis via M2 Polarization

In addition to breaking down food, mastication plays regulatory roles in tissue homeostasis. During mastication, the oral mucosa is subjected to masticatory stress, and the maintenance between mucosal damage and repair is a key process. Despite rapid healing in the oral mucosa during chewing, the molecular mechanisms underlying repair remain unclear. In this study, we investigated the impact of masticatory stress on masticatory mucosal wound healing. Our data showed that reduced masticatory stress on the oral mucosa in mice fed a soft food diet resulted in decelerated hard palate mucosal wound healing and decreased numbers of Ki67-positive cells as compared with the hard food diet group. An RNA sequencing analysis revealed lower expression levels of the mechanosensitive gene <i>Piezo1</i> in the hard palate mucosa, as well as lower levels of transforming growth factor β1 (<i>Tgf-β1</i>) and Tgf-β receptor 2 (<i>Tgf-βr2</i>), in the soft food diet group than the hard food diet group. Immunofluorescence staining, flow cytometry, and polymerase chain reaction analyses demonstrated that masticatory stress induced M2 polarization of macrophages surrounding the wound in the hard food diet group, leading to increased Tgf-β1 secretion. The specific deletion of <i>Piezo1</i> in macrophages (<i>Piezo1</i>^DLysm) attenuated masticatory stress-induced accelerated healing in mice. These findings reveal the crucial role of masticatory stress-induced <i>Piezo1</i> expression in tissue repair, potentially influencing M2 polarization of mucosal macrophages and Tgf-β1 secretion. These findings underscore the pivotal role of physical stimulation in the immune response and tissue repair and may provide important insights into therapeutic interventions for tissue repair.