{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T10:59:33Z","timestamp":1791197973272,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"55","license":[{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T00:00:00Z","timestamp":1783987200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471016"],"award-info":[{"award-number":["82471016"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Advanced Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Protein lactylation is an emerging lactate\u2010derived modification, coupling metabolic reprogramming to inflammatory regulation while modulating cellular responses to the microenvironment. However, the role of macrophage lactylation in orthodontic tooth movement (OTM) remains unclear. Transcriptomic and metabolomic profiling of compressed macrophages identified glycolytic reprogramming as the core regulatory axis, with elevated lactate levels validated in macrophages, mice, and human saliva. Exogenous lactate promoted M1 polarization and NF\u2010\u03baB signaling activation in compressed macrophages, identifying lactate dehydrogenase A (LDHA) as a critical regulatory node. Myeloid\u2010specific\n                    <jats:italic>Ldha<\/jats:italic>\n                    deficiency inhibited OTM and attenuated sterile inflammation, confirming the critical link between lactate metabolism and OTM progression. Mechanistically, we utilized lactylation proteomics and identified that lactate induces specific lactylation of TRAF6 at lysine residues 171, 180, and 388 (K171, K180, K388). Molecular dynamics simulations and site\u2010directed mutagenesis revealed that K171\/K180 lactylation enhances TRAF6 K63\u2010linked ubiquitination, thereby driving NF\u2010\u03baB signaling activation. Consistently, mutation of K171 and K180 diminished TRAF6 K63\u2010linked ubiquitination and suppressed NF\u2010\u03baB activation. Collectively, our findings demonstrate that sustained compressive force reprograms macrophage metabolism toward glycolysis and drives lactylation of TRAF6 at K171\/K180, which serves as a core regulatory node that amplifies NF\u2010\u03baB signaling, thereby facilitating OTM\u2010associated sterile inflammation and alveolar bone remodeling.\n                  <\/jats:p>","DOI":"10.1002\/advs.76518","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T09:55:01Z","timestamp":1784022901000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["TRAF6 Lactylation in Glycolytic Macrophages Drives NF\u2010\u03baB Signaling and M1 Polarization During Orthodontic Tooth Movement"],"prefix":"10.1002","volume":"13","author":[{"given":"Xinyi","family":"He","sequence":"first","affiliation":[{"name":"College of Stomatology Chongqing Medical University  Chongqing China"},{"name":"Chongqing Key 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