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Fig. 6 | Arthritis Research & Therapy

Fig. 6

From: Activating enhancer binding protein 2 epsilon (AP-2ε)-deficient mice exhibit increased matrix metalloproteinase 13 expression and progressive osteoarthritis development

Fig. 6

Enhanced osteoarthritis progression in Tfap2e −/− mice. a In 6- to 8-week-old wild-type (WT) and Tfap2e −/− mice, osteoarthritis (OA) was induced in the right knee joint by detaching the medial meniscus (DMM). In the corresponding left knee joint, a control surgery was performed (Sham). Ten days after surgery, all mice showed only minimal signs of OA. Seventeen days after disease onset, WT mice exhibited low to moderate OA scores, whereas OA severity in Tfap2e −/− mice was significantly enhanced at this time point. b Visible damage to the articular cartilage tissue at day 17 after DMM surgery included wear, lesions and inhomogeneous staining (right, arrowheads). Cartilage of the sham joints had a smooth surface and featured no signs of OA (left). Slides of the top three rows were stained with Safranin O/Fast Green. In the bottom row, further examples of the cartilage surface after staining with hematoxylin and eosin are shown. c Immunohistochemistry with an antiserum raised against the C1,2C collagen cleavage neoepitope was performed to confirm matrix metalloproteinase (MMP)-mediated extracellular matrix degradation and thus development of an OA-like phenotype in response to the DMM treatment. Here, positive staining at the articular cartilage surface could be detected in the DMM joints (arrowheads), whereas this was not the case in the sham joints. The specificity of the staining was controlled with Tfap2e −/− sections without primary antibody treatment (indicated by a “-”), and sections of human OA cartilage were used as positive controls. d Total RNA from the murine articular cartilage layer was isolated 10 and 17 days after OA induction, and expression of activating enhancer binding protein 2, epsilon (AP-2ε) was analyzed in knee joints of WT mice 10 and 17 days after OA onset relative to untreated WT knee joints. A significant induction in the expression rate of the transcription factor could be measured in the articular cartilage of the DMM joints. The data are given as box-and-whisker plots with minimum and maximum values in (a) and as the means ± standard errors of the mean in (d). ns, Not significant; Tfap2e −/−, Deficient for activating enhancer binding protein 2, epsilon. *P < 0.05; **P < 0.01; ***P < 0.001. Numbers indicate individual animals per group

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