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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 Piezo1 in the hard palate mucosa, as well as lower levels of transforming growth factor \u03b21 ( Tgf-\u03b21) and Tgf-\u03b2 receptor 2 ( Tgf-\u03b2r2), 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-\u03b21 secretion. The specific deletion of Piezo1 in macrophages ( Piezo1\n                    <jats:sup>DLysm<\/jats:sup>\n                    ) attenuated masticatory stress\u2013induced accelerated healing in mice. These findings reveal the crucial role of masticatory stress\u2013induced Piezo1 expression in tissue repair, potentially influencing M2 polarization of mucosal macrophages and Tgf-\u03b21 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.\n                  <\/jats:p>","DOI":"10.1177\/00220345241290778","type":"journal-article","created":{"date-parts":[[2024,12,20]],"date-time":"2024-12-20T23:42:53Z","timestamp":1734738173000},"page":"299-309","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":7,"title":["Masticatory Stress Maintains Mucosal Homeostasis via M2 Polarization"],"prefix":"10.1177","volume":"104","author":[{"given":"M.Z.","family":"Ning","sequence":"first","affiliation":[{"name":"Beijing Laboratory of Oral Health and Beijing Stomatological Hospital, Capital Medical University, Beijing, China"},{"name":"Department of Stomatology, Beijing Bo\u2019ai Hospital, China Rehabilitation Research Center, School of Rehabilitation, Capital Medical University, 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