{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:27:30Z","timestamp":1790767650492,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004763","name":"Natural Science Foundation of Inner Mongolia Autonomous Region","doi-asserted-by":"publisher","award":["2025LHMS08054"],"award-info":[{"award-number":["2025LHMS08054"]}],"id":[{"id":"10.13039\/501100004763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aging Cell"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Advanced glycation end products (AGEs) accumulate with aging and metabolic stress and are increasingly implicated in osteoarthritis (OA) pathology. However, how AGEs regulate osteoclast\u2013chondrocyte signaling remains poorly defined. Here, we integrated proteomic and transcriptomic analyses with machine learning to identify molecular networks altered by AGEs in osteoclasts. SIRT1 emerged as a central regulator suppressed following AGE exposure. Loss of SIRT1 deacetylase activity activated the RANKL\/RANK signaling pathway and enhanced osteoclast differentiation. Pharmacological inhibition of RAGE or shRNA\u2010mediated gene silencing restored SIRT1 expression, confirming the upstream role of AGE\u2013RAGE signaling. In a co\u2010culture system, AGE\u2010treated osteoclasts accelerated chondrocyte senescence, as evidenced by elevated senescence markers and SASP factors. Findings were validated in\u00a0vivo, where AGEs aggravated cartilage degeneration, subchondral bone alterations, and chondrocyte senescence in an OA mouse model. Collectively, these results identify an AGE\u2010driven SIRT1\/RANKL axis that links osteoclast activation with chondrocyte aging, highlighting a critical pathway contributing to joint deterioration. Targeting this mechanism may offer new therapeutic opportunities for delaying age\u2010related OA progression.<\/jats:p>","DOI":"10.1111\/acel.70515","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T03:13:00Z","timestamp":1777691580000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>SIRT1<\/scp>\n                    Downregulation by Advanced Glycation End Products Activates\n                    <scp>RANKL<\/scp>\n                    \u2010Dependent Osteoclast Signaling and Drives Chondrocyte Senescence During Osteoarthritis Development"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5511-5097","authenticated-orcid":false,"given":"Yizhou","family":"Li","sequence":"first","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Wu","sequence":"additional","affiliation":[{"name":"General Internal Medicine (Rheumatology and Immunology Specialty) The Second Affiliated Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Orthopedics The First Affiliated Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8070-8836","authenticated-orcid":false,"given":"Fei","family":"Xue","sequence":"additional","affiliation":[{"name":"Area A of Trauma and Orthopedics Department (Geriatric Orthopedics Department) The Second Affiliated Hospital of Inner Mongolia Medical University  Hohhot Inner Mongolia Autonomous Region China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,1]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.08.066"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2023.09.075"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41413\u2010018\u20100040\u20109"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12986\u2010018\u20100306\u20107"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20100716\u20103354\u20100_15"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2021.12.008"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2023.109827"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.12122\/j.issn.1673\u20104254.2020.04.20"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1538662"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2022.04.002"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1302\/2046\u20103758.115.BJR\u20102021\u20100334.R1"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19\u201000036"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586\u2010018\u20100482\u20107"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.4235\/agmr.21.0053"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010022\u201035424\u2010w"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2022.08.020"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/0113862073264389231101190637"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.20935\/acadbiol7428"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2010.203"},{"key":"e_1_2_13_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2022.806842"},{"key":"e_1_2_13_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107141"},{"key":"e_1_2_13_23_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.0904033"},{"key":"e_1_2_13_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S489613"},{"key":"e_1_2_13_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201018208\u2010y"},{"key":"e_1_2_13_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2018.02.015"},{"key":"e_1_2_13_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms10091848"},{"key":"e_1_2_13_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/biology13110848"},{"key":"e_1_2_13_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.198713"},{"key":"e_1_2_13_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.berh.2009.08.006"},{"key":"e_1_2_13_31_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0254268"},{"key":"e_1_2_13_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17071019"},{"key":"e_1_2_13_33_1","doi-asserted-by":"publisher","DOI":"10.1089\/met.2009.0110"},{"key":"e_1_2_13_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2024.102429"},{"key":"e_1_2_13_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/03008207.2016.1177036"},{"key":"e_1_2_13_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12951\u2010022\u201001697\u2010y"},{"key":"e_1_2_13_37_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00264\u2010023\u201005847\u20101"},{"key":"e_1_2_13_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.06.013"},{"key":"e_1_2_13_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11010\u2010018\u20103477\u20107"},{"key":"e_1_2_13_40_1","doi-asserted-by":"publisher","DOI":"10.1159\/000521720"},{"key":"e_1_2_13_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392\u2010023\u201001330\u2010w"},{"key":"e_1_2_13_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00774\u2010020\u201001175\u20101"},{"key":"e_1_2_13_43_1","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.12471"},{"key":"e_1_2_13_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107282"}],"container-title":["Aging Cell"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70515","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/acel.70515","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/acel.70515","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T22:19:10Z","timestamp":1779401950000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/acel.70515"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":43,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1111\/acel.70515"],"URL":"https:\/\/doi.org\/10.1111\/acel.70515","archive":["Portico"],"relation":{},"ISSN":["1474-9718","1474-9726"],"issn-type":[{"value":"1474-9718","type":"print"},{"value":"1474-9726","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-11-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70515"}}