Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival

摘要: OPN is a multifunctional cytokine and adhesion protein that contains an integrin-binding RGD sequence additional sequences interact with CD44v6/7 or other adhesive receptors. Its expression increased in response to early proinflammatory cytokines mechanical strain bone. The function of the secreted may be altered by extracellular enzymes, including thrombin kinases. study OPN-null mice has revealed roles for broad range homeostatic (bone remodeling, tissue debridement) pathologic (cellular immunity, wound healing, cancer metastasis) processes. While these processes seem disparate, they are linked several common themes, enhanced stress injury, stimulation cell motility survival pathways via interactions receptors. OPN chemotactic various types, notably monocytes/macrophages, which attracted sites infection inflammation. It essential cell-mediated immunity normal Th1 during granuloma formation. serves both attach bone cells matrix generate intracellular signals osteoclast on bone; it mediate osteocyte recognition strain. activates signaling regulates gene as consequence its best-characterized integrin-stimulated FAK-Src-Rho pathway, alters gelsolin podosome formation osteoclasts. Identification dissection signal transduction their targets complicated fact can engage more than one type receptor cell. For this reason, important ascertain receptors play any given experimental system. There compelling evidence soluble variety situations help survive otherwise lethal insult. Remarkably, mediated generally considered ECM components. We suggest delivers antiapoptotic “ECM-like” multiple ligand-receptor cells, adherent nonadherent.