without apparent structural changes during the experimental period. Aberrant expression of mRNAs for specific matrix-degrading enzymes, pro-inflammatory cytokines, and major collagens in articular cartilage also displayed a dose-dependent changes at each time point, namely, most severe changes in the Nfat1-/and least remarkable changes in the Nfat1Tg knees. No sex differences were identified. Conclusions: The results support our hypothesis that NFAT1 deficiency accelerates the progression of PTOA in an Naft1 dose-dependent manner, while cartilage-specific Nfat1 overexpression delays the time of onset and attenuates the severity of PTOA in mice. The results from Nfat1þ/mice are particularly important as they reflect the effect of Nfat1 "gene dosage" on PTOA, which will direct us to investigate if a decrease in NFAT1 expression in joint tissues is a risk factor for development of OA in humans. Our novel finding that cartilage-specific NFAT1 overexpression protects articular cartilage against OA may promote the development of new OA therapies using NFAT1 as a molecular target.Purpose: There is growing interest in the association between OA and metabolic syndrome components, specifically systolic blood pressure (SBP) and diastolic blood pressure (DBP). Studies to date have focused on radiographic measures of knee OA and few have utilized magnetic resonance imaging (MRI) markers of knee cartilage composition and morphological knee abnormalities. This study was undertaken to evaluate the relationship of blood pressure (SBP, DBP) with spatial cartilage composition and structural knee abnormalities, assessed using MRI-based grey-level co-occurrence matrix (GLCM) texture analysis of knee cartilage T2 maps and modified whole-organ magnetic resonance imaging scores (WORMS), respectively, in study participants from the Osteoarthritis Initiative (OAI) cohort. Methods: 1,139 study participants were selected from the OAI. The inclusion criteria were right knee Kellgren Lawrence (KL) score 0-2 at baseline, no history of rheumatoid arthritis at baseline, blood pressure measurements available at baseline, cartilage T2 measurements available in at least three knee regions at baseline and 48-month follow-up. Cartilage segmentation of 3 Tesla right knee MR studies was previously performed in five regions (patella, lateral femur, medial femur, lateral tibia and medial tibia). T2 maps were generated and texture parameters (contrast, entropy, variance) were obtained using GLCM analysis, which reflects the heterogeneity of T2 values throughout the cartilage matrix. Global values were computed as the mean of all compartments. Using the semi-quantitative modified WORMS, the following structures were previously graded: cartilage, menisci, ligaments, bone marrow edema pattern (BMEP), subarticular cysts, effusion, loose bodies and popliteal cysts. For each structure, a WORMS subscore was calculated by adding the lesion scores of all subregions of the knee and the overall WORMS score was obtained by adding these subscores. Linear regression mo...
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