{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T23:24:39Z","timestamp":1793402679181,"version":"4.5.0"},"reference-count":71,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"6819","funder":[{"DOI":"10.13039\/501100003716","name":"Korea Basic Science Institute","doi-asserted-by":"publisher","award":["RS-2025-02413415"],"award-info":[{"award-number":["RS-2025-02413415"]}],"id":[{"id":"10.13039\/501100003716","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004085","name":"Ministry of Education, Science and Technology","doi-asserted-by":"publisher","award":["RS-2025-02413415"],"award-info":[{"award-number":["RS-2025-02413415"]}],"id":[{"id":"10.13039\/501100004085","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2019R1A5A2027521"],"award-info":[{"award-number":["2019R1A5A2027521"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["2021R1A2C3005727"],"award-info":[{"award-number":["2021R1A2C3005727"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2024-00454010"],"award-info":[{"award-number":["RS-2024-00454010"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2026-25489708"],"award-info":[{"award-number":["RS-2026-25489708"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2025-02214129"],"award-info":[{"award-number":["RS-2025-02214129"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014188","name":"Ministry of Science and ICT, South Korea","doi-asserted-by":"publisher","award":["RS-2026-25489708"],"award-info":[{"award-number":["RS-2026-25489708"]}],"id":[{"id":"10.13039\/501100014188","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Science"],"published-print":{"date-parts":[[2026,10,1]]},"abstract":"<jats:p>Osteoarthritis (OA) is a degenerative joint disease, the progression of which is accelerated by systemic metabolic stress. Here, we identified a neuroendocrine pathway through which hypertension accelerates OA pathogenesis in joints predisposed by mechanical injury or aging. Nationwide cohort analyses and hypertensive mouse models demonstrated that elevated blood pressure exacerbates OA pathogenesis. OA-primed chondrocytes up-regulated arginine vasopressin (AVP) receptor 1A (AVPR1A), rendering them responsive to hypertension-associated circulating AVP. AVP-AVPR1A signaling enhanced catabolic signaling while suppressing anabolic regulators, thereby promoting cartilage catabolism. Genetic deletion or pharmacological inhibition of AVPR1A protected against hypertension-driven OA acceleration. Transcriptomic profiling and gene-silencing analyses identified NR4A3 as the principal downstream transcriptional mediator. Collectively, these findings establish the AVP-AVPR1A axis as a mechanistic link between systemic hypertensive stress and joint degeneration.<\/jats:p>","DOI":"10.1126\/science.aed8207","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:00:47Z","timestamp":1790877647000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Hypertension fuels osteoarthritis through neuroendocrine signaling"],"prefix":"10.1126","volume":"394","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-9641-7531","authenticated-orcid":true,"given":"Su-Jin","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3773-7574","authenticated-orcid":true,"given":"Hyo-Eun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Future R&amp;D Planning Initiatives, Inje University, Gimhae, Gyeongnam, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0395-2344","authenticated-orcid":true,"given":"Ki-Ho","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Preventive and Public Health Dentistry, Chonnam National University School of Dentistry, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5258-9166","authenticated-orcid":true,"given":"Gyuseok","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3045-8288","authenticated-orcid":true,"given":"Ka Hyon","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8085-7319","authenticated-orcid":true,"given":"Young-Gwon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3491-3217","authenticated-orcid":true,"given":"Mangeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7520-3974","authenticated-orcid":true,"given":"Weon-Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1191-4264","authenticated-orcid":true,"given":"Soo-Chang","family":"Joo","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9774-4828","authenticated-orcid":true,"given":"Hae Jin","family":"Kee","sequence":"additional","affiliation":[{"name":"Cardiovascular Convergence Research Center, Chonnam National University Hospital, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7883-5444","authenticated-orcid":true,"given":"Seung-Hee","family":"Kwon","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6920-5659","authenticated-orcid":true,"given":"Jong-Keun","family":"Seon","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Chonnam National University Hospital, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9155-6498","authenticated-orcid":true,"given":"Gun-Woo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Chonnam National University Hospital, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4098-8370","authenticated-orcid":true,"given":"Yoonkyung","family":"Won","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6279-6487","authenticated-orcid":true,"given":"Jeong-Tae","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1859-3425","authenticated-orcid":true,"given":"Jin","family":"Han","sequence":"additional","affiliation":[{"name":"Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2910-181X","authenticated-orcid":true,"given":"Jang-Soo","family":"Chun","sequence":"additional","affiliation":[{"name":"Future R&amp;D Planning Initiatives, Inje University, Gimhae, Gyeongnam, Republic of Korea."},{"name":"Cardiovascular and Metabolic Disease Center, College of Medicine, Inje University, Busan, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8708-8943","authenticated-orcid":true,"given":"Je-Hwang","family":"Ryu","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Dental Therapeutics, School of Dentistry, Chonnam National University, Gwangju, Republic of Korea."},{"name":"Dental Science Research Institute, Chonnam National University, Gwangju, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-025-00594-6"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2665-9913(23)00163-7"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.135"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.11.012"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-023-00301-9"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.23788"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11926-019-0868-z"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar4405"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-023-01613-9"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-0920-1"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2012.06.006"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0165325"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.05.003"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.semarthrit.2024.152544"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000007584"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2021.11.007"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/8065838"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/kem191"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00650-x"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-021-00147-z"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2006.01.003"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2015.18"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11906-018-0823-9"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.113.003072"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01311"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2007.03.006"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.130"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2153"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.01.007"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc12-2165"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60695-9"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0149-2918(96)80061-0"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.22337"},{"key":"e_1_3_2_35_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.25002"},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2012.02303.x"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.103.061200"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00776-011-0157-9"},{"key":"e_1_3_2_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10067-017-3656-z"},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1111\/jgs.16022"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2025.112938"},{"key":"e_1_3_2_42_2","doi-asserted-by":"publisher","DOI":"10.1002\/ejp.70234"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pmn.2021.08.002"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-025-02365-6"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1111\/jch.12145"},{"key":"e_1_3_2_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(00)00304-0"},{"key":"e_1_3_2_47_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-022-00749-9"},{"key":"e_1_3_2_48_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2023.06.005"},{"key":"e_1_3_2_49_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYP.0000000000000257"},{"key":"e_1_3_2_50_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.124.042132"},{"key":"e_1_3_2_51_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells11193173"},{"key":"e_1_3_2_52_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-48797-8"},{"key":"e_1_3_2_53_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00017.2022"},{"key":"e_1_3_2_54_2","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10091985"},{"key":"e_1_3_2_55_2","doi-asserted-by":"publisher","DOI":"10.1210\/me.2010-0015"},{"key":"e_1_3_2_56_2","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.14804"},{"key":"e_1_3_2_57_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2022.11.001"},{"key":"e_1_3_2_58_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4000"},{"key":"e_1_3_2_59_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00178.2023"},{"key":"e_1_3_2_60_2","doi-asserted-by":"publisher","DOI":"10.1530\/JOE-22-0032"},{"key":"e_1_3_2_61_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.119.14089"},{"key":"e_1_3_2_62_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa065181"},{"key":"e_1_3_2_63_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.122.19222"},{"key":"e_1_3_2_64_2","doi-asserted-by":"publisher","DOI":"10.1097\/BOR.0000000000000373"},{"key":"e_1_3_2_65_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1583"},{"key":"e_1_3_2_66_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2010.05.025"},{"key":"e_1_3_2_67_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0174294"},{"key":"e_1_3_2_68_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.2006.02508.x"},{"key":"e_1_3_2_69_2","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.123.22329"},{"key":"e_1_3_2_70_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2008.95"},{"key":"e_1_3_2_71_2","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12771"},{"key":"e_1_3_2_72_2","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2006.85"}],"container-title":["Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.science.org\/doi\/pdf\/10.1126\/science.aed8207","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T18:00:50Z","timestamp":1790877650000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.science.org\/doi\/10.1126\/science.aed8207"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,1]]},"references-count":71,"journal-issue":{"issue":"6819","published-print":{"date-parts":[[2026,10,1]]}},"alternative-id":["10.1126\/science.aed8207"],"URL":"https:\/\/doi.org\/10.1126\/science.aed8207","relation":{},"ISSN":["0036-8075","1095-9203"],"issn-type":[{"value":"0036-8075","type":"print"},{"value":"1095-9203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,1]]},"assertion":[{"value":"2025-12-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-17","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"eaed8207"}}