ArticleMediators of inflammation2026
Combination of High-Fat Diet and Chronic Unpredictable Stress Synergistically Induces Osteoarthritis-Like Changes in Temporomandibular Joints in Rats.
Article in Mediators of inflammation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
objectivesHigh-fat 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.
methodsMale Sprague-Dawley 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-induced TMJOA-like changes. Serum proteins or lipids were measured by enzyme-linked immunosorbent assay (ELISA) or biochemical analysis. Pathological changes were evaluated using microcomputed tomography (micro-CT) for subchondral bone morphometry, histology with Mankin scoring for cartilage degradation, and TUNEL assays for chondrocyte apoptosis. The expression levels of TLR4, NF-κB p65, and IL-1β in condylar cartilage were assessed by immunofluorescence.
resultsThe HFD/CUS group showed serum levels of total cholesterol (TC), triglycerides, and oxidized LDL (ox-LDL) 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-like 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-like changes at 10 weeks posttreatment. The HFD/CUS group also showed a higher number of TLR4-positive cells, NF-κB p65-nuclear-positive cells, and IL-1β-positive 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.
conclusionHFD and CUS could synergistically induce TMJOA-like changes, potentially by activating the TLR4/NF-κB/IL-1β inflammatory signaling pathway. Our findings suggest an important interplay between metabolic and psychological factors in the pathogenesis of TMJOA.
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