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Coagulation cascade with Factor VII lipoprotein lipase; cleaves triglycerides arachidonate 5-lipoxygenase; catalyzes leukotriene synthesis toll-like receptor 4; LPS receptor vascular cell adhesion molecule 1; immune response prostaglandin E synthase; prostaglandin synthesis, inflammatory responses, discomfort perception phospholipase D2; cleaves phosphatidyl choline suppressor of cytokine signaling three; unfavorable regulator of inflammatory response NF-kB inhibitor, alpha; inhibitor of NF-kB- IkBa tenascin N; cartilage and bone formation periostin; osteoblast precise factor; cell adhesion, mineralization lumican; collagen fibril organization collagen type XVIII a1; a IL-17 Proteins Purity & Documentation potent antiangiogenic collagen variety IV a1; inhibits endothelial proliferation/angiogenesis collagen kind III a1; soft tissue related to Collagen form 1 collagen kind XII, a1; fibrillar collagen collagen sort IV a2; inhibits endothelial proliferation/angiogenesis collagen, variety VI, alpha three; linkage of matrix/cell collagen, kind V, alpha 1; fibrillar collagen ADAM metallopeptidase domain 23; nonproteolytic metalloprotease, cell-cell adhesion serpin peptidase inhibitor, clade E1; inhibits plasminogen activator TIMP metallopeptidase inhibitor two; inhibitor of several MMPs matrix metallopeptidase 14; activates progelatinase MMP 2; ECM breakdown in typical physiologic processes matrix metallopeptidase 11; matrix remodeling, vascular invasion ADAMTS two; cleaves tissue propeptides of collagen type I and II cathepsin D; intracellular proteinase inhibitor TGF beta two; cell division and development differentiation PDGF receptor, b polypeptide; angiogenesis, cell proliferation and differentiation oncostatin M receptor; increases cartilage degradation PDGF C; wound healing, proliferation and remodeling osteoglycin; ErbB2/HER2 Proteins supplier Induces bone formation with TGF-beta-1 or TGF-beta-2 epidermal development issue receptor; cell growth/differentiation WNT1 inducible signaling protein 2; bone turnover Group CD CD CD CD Inf Inf Inf Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 Inf2 ECM ECM ECM ECM ECM ECM ECM ECM ECM ECM ECM2 ECM2 ECM2 ECM2 ECM2 ECM2 ECM2 ECM2 GF GF GF GF GF GF GFFold transform OA 5 two.28 1.10 1.71 1.36 1.64 two.14 1.26 1.46 7.33 1.66 2.05 1.36 1.82 two.14 two.69 1.40 1.72 1.69 1.42 15.five five.88 four.09 2.71 1.80 2.02 two.ten 1.39 1.30 1.ten 3.97 3.27 1.38 1.95 1.01 1.11 1.28 1.61 1.26 1.18 1.85 1.04 1.22 1.29 2.65 OA 9 two.22 1.95 1.98 two.60 two.ten 2.40 1.48 4.63 6.00 three.65 two.56 1.58 1.61 1.83 1.82 two.34 two.32 two.09 2.45 18.8 five.05 five.03 3.92 3.03 three.19 three.11 two.12 2.42 1.73 three.56 3.88 2.19 3.29 1.99 1.47 1.62 two.3 two.67 1.77 two.41 two.22 1.19 1.17 five.71 OA 21 two.72 two.56 two.44 2.42 2.98 two.81 2.01 8.59 7.00 four.45 3.14 two.91 2.86 two.85 two.61 two.60 two.49 2.47 two.17 20.9 7.23 five.90 5.66 four.33 3.88 3.42 3.13 2.71 two.12 five.50 4.81 3.07 3.01 two.84 2.39 two.37 2.25 two.63 2.46 2.45 two.15 2.06 two.05 six.Please see Table two for group description. A complete list of those genes is provided in Table S5. doi:ten.1371/journal.pone.0024320.tPLoS A single www.plosone.orgGene Regulation throughout MIA ProgressionFigure six. Molecular networks generated from the genes in every single cluster by Ingenuity Pathways Evaluation. The molecular networks generated from genes in: (A) Cartilage with Grade 1 harm (Cluster I) Immunological illness network, showing upregulation of genes linked to acute/innate immune response; (B) Cartilage with Grade 1 damage (Clusters IV) – Skeletal muscular development and function network, showing downregulation of transcription components and growth things linked to m.

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