{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T11:10:23Z","timestamp":1779189023161,"version":"3.51.4"},"reference-count":45,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T00:00:00Z","timestamp":1779148800000},"content-version":"vor","delay-in-days":138,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82571120"],"award-info":[{"award-number":["82571120"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271000"],"award-info":[{"award-number":["82271000"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471001"],"award-info":[{"award-number":["82471001"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007128","name":"Natural Science Foundation of Shaanxi Province","doi-asserted-by":"publisher","award":["2024ZC-KJXX-123"],"award-info":[{"award-number":["2024ZC-KJXX-123"]}],"id":[{"id":"10.13039\/501100007128","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["International Journal of Dentistry"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Temporomandibular joint osteoarthritis (TMJ OA) is characterized by articular cartilage degeneration involving chondrocyte loss and matrix degradation. However, the underlying mechanisms remain elusive. Hemoglobin (HB) has been identified in chondrocytes and is closely associated with cell survival.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to investigate the role of HB in condylar cartilage degeneration during the early stage of TMJ OA and evaluate the potential protective effects of hydroxyurea (HU), a therapeutic agent used for sickle cell disease, suggesting its promise as a novel therapeutic strategy against OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The TMJ OA model was established in 6\u2010week\u2010old female rats using unilateral anterior crossbite (UAC). ATDC5 chondrocytes were exposed to fluid flow shear stress (FFSS) to mimic OA\u2010like changes in vitro. Histological and immunohistochemical staining, real\u2010time PCR, and Western blot analysis were performed to detect the morphological and molecular changes in condylar cartilage.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results showed a significant downregulation of\n                      <jats:italic>HBA<\/jats:italic>\n                      and\n                      <jats:italic>HBB<\/jats:italic>\n                      alongside cartilage degeneration in the UAC group, characterized by decreased cartilage thickness, degraded cartilage matrix, and increased matrix metalloproteinases (MMPs). FFSS\u2010stimulated chondrocytes also exhibited decreased\n                      <jats:italic>HBA<\/jats:italic>\n                      and\n                      <jats:italic>HBB<\/jats:italic>\n                      expression. Notably, HU treatment enhanced \u03b3\u2010globin gene (\n                      <jats:italic>HBG<\/jats:italic>\n                      ) expression, mitigated FFSS\u2010stimulated chondrocyte degeneration in vitro, and attenuated TMJ OA progression in vivo. Specifically, HU ameliorated the degenerative phenotype in cartilage, increasing matrix content and reducing matrix\u2010degrading enzyme expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings identify HB subunits as novel molecular targets for OA therapy, with HU demonstrating significant chondroprotective efficacy. The study provides mechanistic insights into OA pathogenesis and highlights a promising repurposing therapeutic strategy for clinical intervention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/ijod\/3607127","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:51:32Z","timestamp":1779187892000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Role of Hemoglobin in Temporomandibular Joint Osteoarthritis and the Therapeutic Potential of Hydroxyurea"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1443-0960","authenticated-orcid":false,"given":"Min","family":"Hui","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8960-7037","authenticated-orcid":false,"given":"Zhihua","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-8281-5378","authenticated-orcid":false,"given":"Qinghua","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3965-2452","authenticated-orcid":false,"given":"Ying","family":"Zhan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5782-7234","authenticated-orcid":false,"given":"Yuqian","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-8916-1016","authenticated-orcid":false,"given":"Fan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6084-0509","authenticated-orcid":false,"given":"Lei","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2464-361X","authenticated-orcid":false,"given":"Mian","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-2208","authenticated-orcid":false,"given":"Hongxu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8428-1249","authenticated-orcid":false,"given":"Shibin","family":"Yu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6871-307X","authenticated-orcid":false,"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2026,5,19]]},"reference":[{"key":"e_1_2_11_1_2","doi-asserted-by":"crossref","first-page":"666","DOI":"10.1016\/j.joca.2024.02.007","article-title":"miR-708-5p Deficiency Involves the Degeneration of Mandibular Condylar Chondrocytes via the TLR4\/NF-\u03baB Pathway","volume":"32","author":"Xu L.","year":"2024","journal-title":"Osteoarthritis Cartilage"},{"key":"e_1_2_11_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24010171"},{"key":"e_1_2_11_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcna.2019.10.007"},{"key":"e_1_2_11_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcmd.2017.10.006"},{"key":"e_1_2_11_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11051330"},{"key":"e_1_2_11_6_2","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1195647"},{"key":"e_1_2_11_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-94782-5"},{"key":"e_1_2_11_8_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0171084"},{"key":"e_1_2_11_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10286-020-00668-3"},{"key":"e_1_2_11_10_2","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.656626"},{"key":"e_1_2_11_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-023-06611-6"},{"key":"e_1_2_11_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amsu.2021.103085"},{"key":"e_1_2_11_13_2","doi-asserted-by":"publisher","DOI":"10.7860\/JCDR\/2017\/23524.9130"},{"key":"e_1_2_11_14_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.080505"},{"key":"e_1_2_11_15_2","doi-asserted-by":"publisher","DOI":"10.11607\/jop.1082"},{"key":"e_1_2_11_16_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034517748562"},{"key":"e_1_2_11_17_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-06-292078"},{"key":"e_1_2_11_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-41769-7"},{"key":"e_1_2_11_19_2","doi-asserted-by":"publisher","DOI":"10.1080\/17512433.2024.2390915"},{"key":"e_1_2_11_20_2","doi-asserted-by":"publisher","DOI":"10.22514\/jofph.2025.025"},{"key":"e_1_2_11_21_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V81.6.1630.1630"},{"key":"e_1_2_11_22_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111464"},{"key":"e_1_2_11_23_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198404053101401"},{"key":"e_1_2_11_24_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2023.284633"},{"key":"e_1_2_11_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0922-3371(90)90079-C"},{"key":"e_1_2_11_26_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.1997.12.8.1174"},{"key":"e_1_2_11_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jex2.70004"},{"key":"e_1_2_11_28_2","doi-asserted-by":"publisher","DOI":"10.3390\/molecules30020385"},{"key":"e_1_2_11_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23169088"},{"key":"e_1_2_11_30_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0024363"},{"key":"e_1_2_11_31_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2012.36"},{"key":"e_1_2_11_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27443"},{"key":"e_1_2_11_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.27002"},{"key":"e_1_2_11_34_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.22.01935"},{"key":"e_1_2_11_35_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2021012743"},{"key":"e_1_2_11_36_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2019000428"},{"key":"e_1_2_11_37_2","first-page":"93","article-title":"Hydroxyurea Ameliorates Mouse Hypoxia Through Inducing Embryonic Hemoglobin","volume":"45","author":"Zhou X.","year":"2023","journal-title":"Journal of Army Medical University"},{"key":"e_1_2_11_38_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020007645"},{"key":"e_1_2_11_39_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2119760"},{"key":"e_1_2_11_40_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24872"},{"key":"e_1_2_11_41_2","volume-title":"Hydroxyurea [Internet]","author":"Memorial Sloan Kettering Cancer Center","year":"2022"},{"key":"e_1_2_11_42_2","doi-asserted-by":"crossref","first-page":"6","DOI":"10.4103\/jpbs.jpbs_482_24","article-title":"Observational Study on Hematological Adverse Drug Reactions (HADRs) From Hydroxyurea in Pediatric Patients With Sickle Cell Disease (SCD): Assessing Prevalence, Causality, Severity, Preventability, and Predictability, Along With Clinical Management by a Clinical Pharmacist at a Tertiary Care Teaching Hospital","volume":"17","author":"Hadia R.","year":"2025","journal-title":"Journal of Pharmacy & Bioallied Sciences"},{"key":"e_1_2_11_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/tera.1420110205"},{"key":"e_1_2_11_44_2","doi-asserted-by":"publisher","DOI":"10.1186\/s10020-025-01184-8"},{"key":"e_1_2_11_45_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200316672"}],"container-title":["International Journal of Dentistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijod\/3607127","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1155\/ijod\/3607127","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1155\/ijod\/3607127","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T10:51:34Z","timestamp":1779187894000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1155\/ijod\/3607127"}},"subtitle":[],"editor":[{"given":"Hannah","family":"Wesley","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1155\/ijod\/3607127"],"URL":"https:\/\/doi.org\/10.1155\/ijod\/3607127","archive":["Portico"],"relation":{},"ISSN":["1687-8728","1687-8736"],"issn-type":[{"value":"1687-8728","type":"print"},{"value":"1687-8736","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2026-01-10","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-19","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"3607127"}}