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 Osteopontin: a multifunctional molecule regulating chronic inflammation and  vascular disease Scatena M; Liaw L; Giachelli CMArterioscler Thromb Vasc Biol  2007[Nov]; 27 (11): 2302-9Osteopontin (OPN) is a multifunctional molecule highly expressed in chronic  inflammatory and autoimmune diseases, and it is specifically localized in and  around inflammatory cells. OPN is a secreted adhesive molecule, and it is thought  to aid in the recruitment of monocytes-macrophages and to regulate cytokine  production in macrophages, dendritic cells, and T-cells. OPN has been classified  as T-helper 1 cytokine and thus believed to exacerbate inflammation in several  chronic inflammatory diseases, including atherosclerosis. Besides proinflammatory  functions, physiologically OPN is a potent inhibitor of mineralization, it  prevents ectopic calcium deposits and is a potent inducible inhibitor of vascular  calcification. Clinically, OPN plasma levels have been found associated with  various inflammatory diseases, including cardiovascular burden. It is thus  imperative to dissect the OPN proinflammatory and anticalcific functions. OPN  recruitment functions of inflammatory cells are thought to be mediated through  its adhesive domains, especially the arginine-glycine-aspartate (RGD) sequence  that interacts with several integrin heterodimers. However, the integrin  receptors and intracellular pathways mediating OPN effects on immune cells are  not well established. Furthermore, several studies show that OPN is cleaved by at  least 2 classes of proteases: thrombin and matrix-metalloproteases (MMPs). Most  importantly, at least in vitro, fragments generated by cleavage not only maintain  OPN adhesive functions but also expose new active domains that may impart new  activities. The role for OPN proteolytic fragments in vivo is almost completely  unexplored. We believe that further knowledge of the effects of OPN fragments on  cell responses might help in designing therapeutics targeting inflammatory and  cardiovascular diseases.|Animals[MESH]|Atherosclerosis/immunology/*physiopathology[MESH]|Calcinosis/physiopathology[MESH]|Humans[MESH]|Inflammation/immunology/*physiopathology[MESH]|Mice[MESH]|Osteopontin/chemistry/*physiology[MESH]|Signal Transduction/physiology[MESH]
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