Antisense targeting of the urokinase receptor blocks urokinase-dependent proliferation, chemoinvasion, and chemotaxis of human synovial cells and chondrocytes in vitro. 1998

G Fibbi, and M Pucci, and U Serni, and M M Cerinic, and M Del Rosso
Institute of General Pathology of Florence University, Firenze, Italy.

Proliferation and invasion of synovial pannus in rheumatoid arthritis and cartilage remodeling in osteoarthritis are key events in development of disability of arthritic joints. The mechanisms that trigger these events are still poorly understood. The production of urokinase-type plasminogen activator (u-PA) by synovial cells and chondrocytes and the subsequent interaction of u-PA with its membrane receptor (u-PAR) is under the control of a variety of growth factors and cytokines released within the inflamed joints. Here we show that u-PA, on interaction with the specific receptor, regulates movement and invasion as well as proliferation of human synovial cells and chondrocytes. Targeting the urokinase receptor with an antisense oligonucleotide blocks the u-PA-dependent synoviocyte and chondrocyte proliferation and chemoinvasion, suggesting a possible use for this new class of drugs in the progression of the disease in rheumatoid arthritis and osteoarthritis.

UI MeSH Term Description Entries
D011956 Receptors, Cell Surface Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands. Cell Surface Receptor,Cell Surface Receptors,Hormone Receptors, Cell Surface,Receptors, Endogenous Substances,Cell Surface Hormone Receptors,Endogenous Substances Receptors,Receptor, Cell Surface,Surface Receptor, Cell
D002358 Cartilage, Articular A protective layer of firm, flexible cartilage over the articulating ends of bones. It provides a smooth surface for joint movement, protecting the ends of long bones from wear at points of contact. Articular Cartilage,Articular Cartilages,Cartilages, Articular
D002455 Cell Division The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION. M Phase,Cell Division Phase,Cell Divisions,Division Phase, Cell,Division, Cell,Divisions, Cell,M Phases,Phase, Cell Division,Phase, M,Phases, M
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D002633 Chemotaxis The movement of cells or organisms toward or away from a substance in response to its concentration gradient. Haptotaxis
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005109 Extracellular Matrix A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere. Matrix, Extracellular,Extracellular Matrices,Matrices, Extracellular
D006131 Growth Inhibitors Endogenous or exogenous substances which inhibit the normal growth of human and animal cells or micro-organisms, as distinguished from those affecting plant growth ( Cell Growth Inhibitor,Cell Growth Inhibitors,Growth Inhibitor,Growth Inhibitor, Cell,Growth Inhibitors, Cell,Inhibitor, Cell Growth,Inhibitor, Growth,Inhibitors, Cell Growth,Inhibitors, Growth
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D012333 RNA, Messenger RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm. Messenger RNA,Messenger RNA, Polyadenylated,Poly(A) Tail,Poly(A)+ RNA,Poly(A)+ mRNA,RNA, Messenger, Polyadenylated,RNA, Polyadenylated,mRNA,mRNA, Non-Polyadenylated,mRNA, Polyadenylated,Non-Polyadenylated mRNA,Poly(A) RNA,Polyadenylated mRNA,Non Polyadenylated mRNA,Polyadenylated Messenger RNA,Polyadenylated RNA,RNA, Polyadenylated Messenger,mRNA, Non Polyadenylated

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