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Bone marrow serves as the powerhouse of neutrophil differentiation, while the state of neutrophil NETosis therein and its relationship with bone aging remains largely elusive. Moreover, it remains unclear how neutrophil heterogeneity and pro\u2010inflammatory cues within bone marrow synergistically regulate neutrophil NETosis. Here, we find neutrophil NETosis is highly activated in the bone marrow of 3\u2010mon male senescence\u2010accelerated mouse prone 6 (SAMP6), and the released NETs induce BMSCs senescence and impairs their osteogenesis. Further, we verify in vivo NETs\u2010clearance significantly ameliorates bone aging of 3\u2010mon male SAMP6 mice. Next, through scRNA\u2010seq we find a CD55\n                    <jats:sup>+<\/jats:sup>\n                    intermediate mature neutrophil subset enriching in the 3\u2010mon male SAMP6 bone marrow, characterized by significantly upregulated NETosis. Through cell transfer, we demonstrate this subset directly induces bone aging. Mechanistically, elevated ROS within the bone marrow of SAMP6 integrates with a CD55\u2010primed HIF1\u0251\u2010PADI4 pathway to trigger NETosis, and senescent BMSCs serve as a ROS\u2010producer. In summary, our results demonstrate that activated NETosis in CD55\n                    <jats:sup>+<\/jats:sup>\n                    intermediate\u2010mature neutrophils plays a key role in initiating bone aging. Also, we uncover the vicious cycle of inflammaging between immune dysregulation and cellular senescence in bone marrow, providing potential targets for osteoporosis treatment.\n                  <\/jats:p>","DOI":"10.1002\/advs.202500046","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:11:58Z","timestamp":1767881518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["ROS Activated NETosis of Bone Marrow CD55\n                    <sup>+<\/sup>\n                    Intermediate Mature Neutrophils Through HIF1\u03b1\u2010PADI4 Pathway to Initiate Bone Aging"],"prefix":"10.1002","volume":"13","author":[{"given":"Yutong","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory For Dental Materials  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengjie","family":"Cui","sequence":"additional","affiliation":[{"name":"Department of General Dentistry Peking University School and Hospital of Stomatology  Beijing P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Orthodontics Peking University School and Hospital of Stomatology &amp; National Center for Stomatology &amp; National Clinical Research Center for Oral Diseases &amp; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices&amp; Beijing Key Laboratory of Digital Stomatology &amp; NHC Key Laboratory of Digital Stomatology &amp; NMPA Key Laboratory For Dental Materials  Beijing P. R. 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