Coagulation cascade with Issue VII lipoprotein lipase; cleaves triglycerides arachidonate 5-lipoxygenase; catalyzes leukotriene synthesis toll-like receptor four; LPS receptor vascular cell adhesion molecule 1; Leukocyte Immunoglobin-Like Receptors Proteins Biological Activity 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; Deubiquitinase Proteins web Cartilage and bone formation periostin; osteoblast specific element; cell adhesion, mineralization lumican; collagen fibril organization collagen type XVIII a1; a potent antiangiogenic collagen kind IV a1; inhibits endothelial proliferation/angiogenesis collagen variety III a1; soft tissue related to Collagen variety 1 collagen kind XII, a1; fibrillar collagen collagen sort IV a2; inhibits endothelial proliferation/angiogenesis collagen, form VI, alpha three; linkage of matrix/cell collagen, variety 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 quite a few MMPs matrix metallopeptidase 14; activates progelatinase MMP two; ECM breakdown in normal 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 2; cell division and growth differentiation PDGF receptor, b polypeptide; angiogenesis, cell proliferation and differentiation oncostatin M receptor; increases cartilage degradation PDGF C; wound healing, proliferation and remodeling osteoglycin; Induces bone formation with TGF-beta-1 or TGF-beta-2 epidermal growth aspect receptor; cell growth/differentiation WNT1 inducible signaling protein two; 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 change OA 5 2.28 1.ten 1.71 1.36 1.64 2.14 1.26 1.46 7.33 1.66 2.05 1.36 1.82 2.14 two.69 1.40 1.72 1.69 1.42 15.5 5.88 4.09 2.71 1.80 two.02 two.ten 1.39 1.30 1.ten three.97 three.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 two.65 OA 9 two.22 1.95 1.98 2.60 two.ten two.40 1.48 four.63 six.00 three.65 2.56 1.58 1.61 1.83 1.82 two.34 2.32 2.09 two.45 18.eight 5.05 five.03 three.92 3.03 3.19 three.11 two.12 two.42 1.73 3.56 three.88 2.19 3.29 1.99 1.47 1.62 two.three two.67 1.77 two.41 two.22 1.19 1.17 5.71 OA 21 two.72 two.56 two.44 2.42 2.98 two.81 two.01 8.59 7.00 4.45 3.14 2.91 two.86 2.85 2.61 2.60 2.49 two.47 two.17 20.9 7.23 5.90 5.66 4.33 3.88 3.42 three.13 2.71 2.12 5.50 4.81 3.07 3.01 two.84 two.39 2.37 two.25 two.63 two.46 2.45 2.15 2.06 2.05 six.Please see Table two for group description. A complete list of these genes is given in Table S5. doi:10.1371/journal.pone.0024320.tPLoS A single www.plosone.orgGene Regulation during MIA ProgressionFigure 6. Molecular networks generated from the genes in every cluster by Ingenuity Pathways Analysis. The molecular networks generated from genes in: (A) Cartilage with Grade 1 damage (Cluster I) Immunological illness network, displaying upregulation of genes related to acute/innate immune response; (B) Cartilage with Grade 1 damage (Clusters IV) – Skeletal muscular improvement and function network, showing downregulation of transcription variables and growth components associated with m.