{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T10:06:53Z","timestamp":1784369213660,"version":"3.55.0"},"reference-count":48,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T00:00:00Z","timestamp":1784332800000},"content-version":"vor","delay-in-days":198,"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":["82170981"],"award-info":[{"award-number":["82170981"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>High\u2010fat diet (HFD) and chronic unpredictable stress (CUS) are potential risk factors for temporomandibular joint osteoarthritis (TMJOA). This study aimed to investigate whether the combination of HFD and CUS synergistically induces pathological changes in the temporomandibular joints (TMJs) and to explore the underlying molecular mechanisms.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Male Sprague\u2010Dawley rats were assigned to four groups as follows normal diet (ND), HFD, ND with CUS (ND\/CUS), and HFD with CUS (HFD\/CUS), and were treated with HFD, CUS, or both accordingly. TMJs were harvested after 5 or 10 weeks of HFD, CUS, or combined HFD\/CUS treatment. An additional group was used to evaluate whether the TLR4 inhibitor TAK242 could attenuate HFD\/CUS\u2010induced TMJOA\u2010like changes. Serum proteins or lipids were measured by enzyme\u2010linked immunosorbent assay (ELISA) or biochemical analysis. Pathological changes were evaluated using microcomputed tomography (micro\u2010CT) for subchondral bone morphometry, histology with Mankin scoring for cartilage degradation, and TUNEL assays for chondrocyte apoptosis. The expression levels of TLR4, NF\u2010\u03baB p65, and IL\u20101\u03b2 in condylar cartilage were assessed by immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The HFD\/CUS group showed serum levels of total cholesterol (TC), triglycerides, and oxidized LDL (ox\u2010LDL) comparable to those in the HFD group, and both groups had significantly higher levels than the ND and ND\/CUS groups. Simultaneously, the HFD\/CUS group also exhibited the earliest and most severe TMJOA\u2010like pathological changes and highest Mankin score, including cartilage degradation, subchondral bone resorption, and increased chondrocyte apoptosis as early as 5 weeks posttreatment. The ND\/CUS and HFD groups only showed slight degenerative changes at 5 weeks posttreatment and obvious TMJOA\u2010like changes at 10 weeks posttreatment. The HFD\/CUS group also showed a higher number of TLR4\u2010positive cells, NF\u2010\u03baB p65\u2010nuclear\u2010positive cells, and IL\u20101\u03b2\u2010positive cells in the condylar chondrocytes than those in the ND\/CUS and HFD groups at 5 weeks posttreatment. TAK242 significantly alleviated the cartilage degradation, subchondral bone destruction, and chondrocyte apoptosis in the HFD\/CUS group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HFD and CUS could synergistically induce TMJOA\u2010like changes, potentially by activating the TLR4\/NF\u2010\u03baB\/IL\u20101\u03b2 inflammatory signaling pathway. Our findings suggest an important interplay between metabolic and psychological factors in the pathogenesis of TMJOA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/1164213","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T09:56:56Z","timestamp":1784368616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Combination of High\u2010Fat Diet and Chronic Unpredictable Stress Synergistically Induces Osteoarthritis\u2010Like Changes in Temporomandibular Joints in Rats"],"prefix":"10.1155","volume":"2026","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-2765-4964","authenticated-orcid":false,"given":"Xi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4667-4556","authenticated-orcid":false,"given":"Ting","family":"Hao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7806-8174","authenticated-orcid":false,"given":"Ye-Hua","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,18]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034515574770"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.15386\/cjmed-485"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0045036"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2011.12.006"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.158874"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.7812\/TPP\/19.144"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-022-01855-8"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2015.09.017"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1111\/head.14322"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/1129-2377-15-63"},{"key":"e_1_2_8_11_2","first-page":"125","article-title":"Psychological Stress Alters Extracellular Matrix Metabolism in Mandibular Condylar Cartilage","volume":"20","author":"Li Q.","year":"2017","journal-title":"The Chinese journal of dental research"},{"key":"e_1_2_8_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.41679"},{"key":"e_1_2_8_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2020.154194"},{"key":"e_1_2_8_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-019-0156-1"},{"key":"e_1_2_8_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2021.06.013"},{"key":"e_1_2_8_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2023.05.014"},{"key":"e_1_2_8_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/odi.14294"},{"key":"e_1_2_8_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2024.117304"},{"key":"e_1_2_8_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.70029"},{"key":"e_1_2_8_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0022034512441946"},{"key":"e_1_2_8_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.archoralbio.2025.106301"},{"key":"e_1_2_8_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112995"},{"key":"e_1_2_8_23_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.yhbeh.2025.105744"},{"key":"e_1_2_8_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/emm.2015.127"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2013.10.016"},{"key":"e_1_2_8_26_2","doi-asserted-by":"publisher","DOI":"10.1253\/circj.CJ-15-0345"},{"key":"e_1_2_8_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202310266"},{"key":"e_1_2_8_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2014.209"},{"key":"e_1_2_8_29_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24076405"},{"key":"e_1_2_8_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.38399"},{"key":"e_1_2_8_31_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2020.104690"},{"key":"e_1_2_8_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2022.09.011"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2016.11.029"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00187257"},{"key":"e_1_2_8_35_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-197052030-00002"},{"key":"e_1_2_8_36_2","doi-asserted-by":"crossref","first-page":"1745","DOI":"10.1016\/S0140-6736(19)30417-9","article-title":"Osteoarthritis","volume":"393","author":"Hunter D. 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