Objective: This study examined whether physical activity (PA) explains the association between dietary inflammatory potential and OA in the elderly. Methods: A total of 1249 elderly people (≥65 years) were eligible for this study from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. The semi-quantitative Food Frequency Questionnaire (FFQ) and Global PA Questionnaire (GPAQ) were used to evaluate the diet and PA of the elderly, respectively. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence interval (CI) between Energy-adjusted Dietary Inflammatory Index (E-DII) and OA. The interaction of E-DII and PA on depressive events was tested, and the mediation analysis of PA was performed. Results: The average E-DII in this study was +0.68 (SE 0.08), and the score ranges from -5.32 (most anti-inflammatory) to +4.26 (most pro-inflammatory). In comparison with the first quartile, the elderly from the second quartile (OR: 1.16 [95% CI: 1.06, 1.68]) to the fourth quartile (OR: 1.64 [ 95% CI: 1.13, 2.37]) had a higher risk of OA before adjustment for PA. An interaction was observed between E-DII and PA in terms of the risk of OA (PInteraction <0.001). The whole related part was mediated by PA (20.08%). Conclusion: Our findings indicate that the higher pro-inflammatory potential of diet is associated with a higher risk of OA, and low PA is an important part of the mediating factor in the relationship between systemic low-grade dietary inflammation and the risk of OA.

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Osteoarthritis (OA) is a degenerative joint disease which lacks effective medical treatment due to ill‐defined molecular mechanisms underlying the pathology. Inflammation is a key factor that induces and aggravates OA. Therefore, the current study aims to explore roles of the dysregulated long non‐coding RNAs in the pro‐inflammatory cytokine IL‐1β‐mediated catabolic effects in cartilage tissue and chondrocytes. We identified RP11‐364P22.2 as dysregulated in OA patient‐derived cartilage tissues and highly responsive to IL‐1β stimulus. RNA pull‐down coupled with mass spectrometry demonstrated that RP11‐364P22.2 physically binds to activating transcription factor 3 (ATF3) and thus increases the protein stability and facilitates its nuclear translocation. Loss‐ and gain‐of‐function assays indicated that the interaction between RP11‐364P22.2 and ATF3 is indispensable for the detrimental effects of IL‐1β including growth inhibition, apoptosis induction as well as degradation of the key chondrocyte structural proteins of type II collage and Aggrecan and synthesis of the extracellular matrix‐degrading enzyme MMP13 in chondrocytes. In vivo, depletion of the RP11‐364P22.2 effector ATF3 drastically prevented OA development in the rats with surgical destabilization of the medial meniscus (DMM). These results highlight the important roles of lncRNAs in the pathogenesis of OA and indicate the RP11‐364P22.2/ATF3 regulatory axis as a potential therapeutic target of inflammation‐induced OA.

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