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Specifically, how macrophages transduce mechanical forces into osteoclastogenic signals remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Our integrated approach combined analyses at multiple levels: clinical analysis of human periodontal ligament (PDL) tissues via qPCR and immunofluorescence; in vivo functional assessment using murine OTM and fracture models with macrophage\u2010specific knockouts (for\n                      <jats:italic>Piezo1<\/jats:italic>\n                      and Z\u2010DNA binding protein 1 (\n                      <jats:italic>Zbp1<\/jats:italic>\n                      ), designated as\n                      <jats:italic>\n                        Piezo1\n                        <jats:sup>cko<\/jats:sup>\n                      <\/jats:italic>\n                      and\n                      <jats:italic>\n                        Zbp1\n                        <jats:sup>cko<\/jats:sup>\n                      <\/jats:italic>\n                      ); and in vitro mechanistic investigation through RNA sequencing of murine bone marrow\u2010derived macrophages (BMDMs) and pharmacological screening. This multi\u2010faceted strategy was employed to dissect the pathway.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Mechanical stress activated macrophage Piezo1, triggering Ca\n                      <jats:sup>2+<\/jats:sup>\n                      influx and subsequent upregulation of ZBP1. This axis was essential for pro\u2010inflammatory cytokine release and osteoclastogenesis. Macrophage\u2010specific deletion of\n                      <jats:italic>Piezo1<\/jats:italic>\n                      or\n                      <jats:italic>Zbp1<\/jats:italic>\n                      significantly decelerated OTM and preserved alveolar bone mass. Notably,\n                      <jats:italic>Zbp1<\/jats:italic>\n                      overexpression rescued the remodelling defects in\n                      <jats:italic>Piezo1<\/jats:italic>\n                      \u2010deficient mice. Virtual screening identified JNJ\u201010311795 as a ZBP1 modulator; its administration effectively slowed OTM and, conversely, accelerated fracture healing by shifting the balance towards bone formation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The Piezo1\u2013ZBP1 axis constitutes a novel mechano\u2010immune switch converting physical stress into inflammation and bone resorption. Pharmacological targeting of this axis offers a bidirectional therapeutic strategy for controlling orthodontic movement and enhancing bone repair.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ctm2.70703","type":"journal-article","created":{"date-parts":[[2026,5,23]],"date-time":"2026-05-23T07:28:35Z","timestamp":1779521315000},"source":"Crossref","is-referenced-by-count":4,"title":["Macrophage piezo1 senses mechanical force to drive osteoclastogenesis via ZBP1: Implications for bone remodelling therapy"],"prefix":"10.1002","volume":"16","author":[{"given":"Linlin","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Orthodontics The Affiliated Stomatological Hospital of Nanjing Medical University  Nanjing Jiangsu China"},{"name":"State Key Laboratory Cultivation Base of Research Prevention and Treatment for Oral Diseases Nanjing Medical University  Nanjing Jiangsu China"},{"name":"Jiangsu Province Engineering Research Center of Stomatological 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