A gene expression study of normal and damaged cartilage in anteromedial gonarthrosis, a phenotype of osteoarthritis  S. Snelling, R. Rout, R. Davidson,

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A gene expression study of normal and damaged cartilage in anteromedial gonarthrosis, a phenotype of osteoarthritis  S. Snelling, R. Rout, R. Davidson, I. Clark, A. Carr, P.A. Hulley, A.J. Price  Osteoarthritis and Cartilage  Volume 22, Issue 2, Pages 334-343 (February 2014) DOI: 10.1016/j.joca.2013.12.009 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 AMG. A. A medial tibial plateau resection specimen from a patient having Unicompartmental knee arthroplasty (UKA) for AMG. The schematic on the right helps better demonstrate the areas of full thickness cartilage loss, partial thickness cartilage loss and macroscopically normal cartilage. B. Schematic representation of AMG. The damaged area can be divided into equal thirds (T1, T2, T3). The undamaged cartilage is region N. T1-T3 and N were collected for microarray analysis. Osteoarthritis and Cartilage 2014 22, 334-343DOI: (10.1016/j.joca.2013.12.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Distribution of up- and down-regulated genes within enriched GO groups. Differentially expressed genes were classified according to their GO group. GO groups that were significantly enriched were selected and the number of genes within each group that were up- or down-regulated in damaged compared to undamaged cartilage was calculated. Genes were included if there expression was showed >2 fold change in expression in all nine individuals with P < 0.05. Unfilled bars represent genes that were expressed at a higher level y in damaged compared to undamaged cartilage. Shaded bars represent those expressed at a lower level in damaged compared to undamaged cartilage. ECR = Extracellular Region. ECM = Extracellular Matrix. Osteoarthritis and Cartilage 2014 22, 334-343DOI: (10.1016/j.joca.2013.12.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Pathway analysis. Ingenuity analysis on differentially expressed genes in damaged and undamaged cartilage revealed three protein–protein interaction networks showing significant association. These were, A. Cellular Development, Skeletal and Muscular System Development and function, Lymphoid tissue structure development. B. Inflammatory response, cell death, haematological disease. C. Skeletal and muscular disorders, cell signalling, small molecule biochemistry Nodes shaded grey are genes with significant expression differences in the microarray. Osteoarthritis and Cartilage 2014 22, 334-343DOI: (10.1016/j.joca.2013.12.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 4 Real-time PCR analysis. RNA was extracted from damaged and undamaged cartilage to confirm expression changes seen in the microarray analysis. Real-time PCR was carried out to assess gene expression of MMP1, MMP3, MMP13, SOX11, IGF1, FGF18 and TNFRSF11B. Osteoarthritis and Cartilage 2014 22, 334-343DOI: (10.1016/j.joca.2013.12.009) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions