Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study investigated whether treatment of articular cartilage chondrocytes with a combination of oncostatin M (OSM) and interleukin-1 (IL-1) could induce a degradative phenotype that was mediated through the protein kinase R (PKR) signalling pathway. High-density monolayer cultures of full depth, bovine chondrocytes were treated with a combination of OSM and IL-1 (OSM+IL-1) for 7 days. To inhibit the activation of PKR, a pharmacological inhibitor of PKR was added to duplicate cultures. Pro- and active matrix metalloproteinase-9 (MMP9) and MMP9 mRNA were significantly upregulated by OSM+IL-1 through a PKR dependent mechanism. ADAMTS4 and ADAMTS5 mRNA were also upregulated by OSM+IL-1. The upregulation of ADAMTS4 and ADAMTS5 were, in part, mediated through PKR. OSM+IL-1 resulted in a loss of type II collagen, which could not be rescued by PKR inhibition. OSM+IL-1 reduced the expression of COL2A1 (type II collagen), COL9A1 (type IX collagen), COL11A1 (type XI collagen), and ACAN (aggrecan) mRNAs. Expression of type II and XI collagen and aggrecan was reduced further when PKR was inhibited. OSM+IL-1 resulted in an 11-fold increase in TNFa mRNA which was, in part, mediated through the PKR pathway. This study demonstrates, for the first time, that a number of catabolic and pro-inflammatory effects known to be important in human arthritis and induced by OSM and IL-1, are mediated by the PKR signalling pathway.
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PMID:Protein kinase R plays a pivotal role in oncostatin M and interleukin-1 signalling in bovine articular cartilage chondrocytes. 2228 13

Osteoarthritis (OA) is one of the most common forms of arthritis world widely. Some key genes and diagnostic markers have been reported due to the development of modern molecular biology technologies. However, the etiology and pathogenesis of OA remains unknown. In this study, an integrated network and pathway analysis towards the biological function of OA-associated genes was conducted to provide valuable information to further explore the etiology and pathogenesis of OA. A total of 2,548 genes which reported a statistically significant association with OA were screened. An integrated network and pathway analysis was performed to identify the pathways and genes most associated to OA. Moreover, OA-specific protein-protein interaction (PPI) network was constructed by cytocluster based on the Molecular Complex Detection Algorithm (MCODE) to screen its candidate biomarkers. Quantitative real-time polymerase chain reaction was used to confirm the expression levels and to validate the results of MCODE cluster analysis by six genes. The pathway networks suggested that extracellular matrix (ECM) organization, collagen degradation and collagen formation showed important associations with OA. In top two PPI clusters, 61 of the OA-associated genes were included in the OA-specific PPI network, which also included 23 candidate genes that are likely to be highly associated with OA based on MCODE clusters. Analysis of mRNA showed that the expression levels of COL9A1, COL9A2, ITGA3, COL9A3, ITGA2, and LAMA1 in the peripheral blood mononuclear cells of OA patients were significantly lower than those of the normal controls (p<0.005). To our knowledge, this is the first comprehensive and systematic report based on OA-related genes demonstrating that the functional destruction of collagen in cartilage may be a very important contributing factor to OA. Quantitative detection of collagen synthesis may be of great help in early identification and prediction of OA. Maintaining the quality and quantity of collagen can be a potential target for clinical treatment of OA in the future practice.
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PMID:Potential candidate biomarkers associated with osteoarthritis: Evidence from a comprehensive network and pathway analysis. 3082 Sep 58