Fibroblast biology - Signals targeting the synovial fibroblast in arthritis

Fibroblast-like cells in the synovial lining (type B lining cells), stroma and pannus tissue are targeted by many signals, such as the following: liga nds binding to cell surface receptors; lipid soluble, small molecular weigh t mediators (eg nitric oxide [NO], prostaglandins, carbon monoxide); extrac ellular matrix (ECM)-cell interactions; and direct cell-cell contacts, incl uding gap junctional intercellular communication. Joints are subjected to c yclic mechanical loading and shear forces. Adherence and mechanical forces affect fibroblasts via the ECM (including the hyaluronan fluid phase matrix ) and the pericellular matrix (eg extracellular matrix metalloproteinase in ducer [EMMPRIN]) matrices, thus modulating fibroblast migration, adherence, proliferation, programmed cell death (including anoikis), synthesis or deg radation of ECM, and production of various cytokines and other mediators [1 ]. Aggressive, transformed or transfected mesenchymal cells containing prot o-oncogenes can act in the absence of lymphocytes, but whether these cells represent regressed fibroblasts, chondrocytes or bone marrow stem cells is unclear.