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Regeneration of soft tissue and alveolar bone is further limited in periodontitis with type 2 diabetes mellitus (T2DM). Low-intensity pulsed ultrasound (LIPUS) has a therapeutic effect on periodontitis, but whether LIPUS can alleviate periodontitis with T2DM is unknown. This research sought to explore the therapeutic effect of LIPUS on periodontitis with T2DM and investigate the mechanism underlying that. The results indicated that the osteogenic differentiation ability of primary human periodontal ligament stem cells (hPDLSCs) in a hyperglycemic inflammatory environment was damaged, and LIPUS restored it. The level of oxidative stress on the hyperglycemic inflammatory environment was increased, and LIPUS attenuated that through the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. In vivo, LIPUS alleviated periodontitis in mice with T2DM through activation of Nrf2. In conclusion, this research shows that LIPUS can promote the osteogenic differentiation ability of hPDLSCs in a hyperglycemic inflammatory environment and alleviate periodontitis in mice with T2DM through the Nrf2 pathway and demonstrates a promising adjuvant treatment strategy for periodontitis with T2DM.<\/jats:p>","DOI":"10.1063\/5.0281678","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T13:07:51Z","timestamp":1760620071000},"update-policy":"https:\/\/doi.org\/10.1063\/aip-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["Low-intensity pulsed ultrasound alleviates periodontitis in mice with T2DM through Nrf2 pathway"],"prefix":"10.1063","volume":"9","author":[{"given":"Yiyao","family":"Hu","sequence":"first","affiliation":[{"name":"College of Stomatology, Chongqing Medical University 1 , Chongqing 401147,","place":["People's Republic of China"]},{"name":"Chongqing Key Laboratory of Oral Diseases, Chongqing 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