{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T13:31:12Z","timestamp":1791725472225,"version":"4.3.4"},"reference-count":39,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T00:00:00Z","timestamp":1762992000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["61200005202318"],"award-info":[{"award-number":["61200005202318"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2025,11,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    With the global rise in osteoporosis due to aging, impaired osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a critical pathogenic factor. Although high mobility group box\u00a02 (HMGB2) is implicated in BMSC aging and organismal senescence, its mechanistic role in osteoporosis remains unclear. Here, we investigate HMGB2's regulatory effects on BMSC osteogenic differentiation under aging conditions. Using an H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010induced BMSC senescence model, we demonstrate that cellular senescence suppresses osteogenic differentiation, evidenced by reduced expression of osteogenic markers and diminished proliferation. Notably, HMGB2 overexpression reversed senescence\u2010mediated osteogenic impairment. In\u00a0vivo studies of ovariectomy\u2010induced aging mice revealed a strong correlation between HMGB2 downregulation and osteoporosis progression, confirmed via immunohistochemistry. Mechanistically, HMGB2 promotes osteogenesis by directly suppressing TNF\u2010\u03b1 and stabilizing the long non\u2010coding RNA TUG1, which subsequently inhibits pro\u2010inflammatory cytokines IL\u20101\u03b2 and IL\u20106. This dual regulatory pathway highlights HMGB2's role in counteracting senescence\u2010driven osteogenic decline. Our study not only elucidates a novel HMGB2\/TUG1 axis governing stem cell differentiation but also identifies HMGB2 as a promising therapeutic target for combating osteoporosis.\n                  <\/jats:p>","DOI":"10.1096\/fj.202500484rrrr","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T09:08:00Z","timestamp":1763024880000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>HMGB2<\/scp>\n                    Deficiency in Bone Marrow Mesenchymal Stem Cells Promotes Age\u2010Related Osteoporosis by Inhibiting Osteoblast Differentiation via Inflammatory Factors"],"prefix":"10.1096","volume":"39","author":[{"given":"Zhiliang","family":"Li","sequence":"first","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuqing","family":"Cai","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Lu","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoshuo","family":"Qian","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxiu","family":"Yan","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongwei","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Mechanical Engineering Shandong University  Jinan China"},{"name":"Shandong Public Health Clinical Center Shandong University  Jinan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6981-0042","authenticated-orcid":false,"given":"Jing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences Shandong University  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.7326\/AITC202401160"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp2307353"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23052701"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21010349"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/13697137.2021.1951697"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202301300"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.101963"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202300488R"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1177\/0963689717721201"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/1566524023666221025104629"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2022.101450"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2024.12.044"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24098334"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11101451"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201608026"},{"key":"e_1_2_9_17_1","first-page":"362","article-title":"Transcriptional Repression of High\u2010Mobility Group Box\u00a02 by p21 in Radiation\u2010Induced Senescence","volume":"41","author":"Kim H. 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