[Osteopontin, a multi-faceted molecule].
Osteopontin (OPN) was initially isolated from bovine bone cortex, as a complex syalilated phospho-glyco-protein of around 60 kDa, with many postranslational modifications. It has been long considered a structural bone protein linking bone cells to the bone extracellular matrix (osteo : bone, pontin : bridge). It has been cloned for the first time in 1986. Since then, it was established that it is part of a protein family called SIBLINGs, which genes share common expression in bone and tooth, and encode among others a RGD motif. OPN is an intracellular as well as secreted protein, which binds to multiple organic or mineral ligands, like the integrin receptor alphaVbeta3, CD44, factor H and hydroxyapatite, depending on its final configuration (phosphorylation state). Pleiotropic functions of osteopontin have been demonstrated, and the osteopontin knock out phenotype in mice gave some new insight on the implication of the molecule in vivo. Osteopontin inhibits mineralization in bone and urine. Besides, it is a strong chemoattractive and proinflammatory molecule, implicated in tumors, like breast or prostate cancers, and in the defense against various infectious agents like tuberculosis, listeria or herpes. More recently, its key implication in TH1 mediated autoimmune diseases like multiple sclerosis and its animal model experimental autoimmune encephalomyelitis has been demonstrated. Osteopontin is a valuable therapeutic target in the animal model, and a biological tool correlating with clinical disease activity in humans. Structural, functional and pathological aspects of osteopontin are reviewed, as well as the osteopontin deficient phenotype in mouse.
Chabas
Dorothée
D
Inserm U.546, Faculté de médecine Pitié-Salpêtrière, Paris, France. dchabas@chups.jussieu.fr
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000503:physiopathology*; D002630:Chemotactic Factors / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D007109:Immunity / Q000502:physiology; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D053495:Osteopontin; D010641:Phenotype; D012795:Sialoglycoproteins / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*
D002630:Chemotactic Factors; D008024:Ligands; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; D053495:Osteopontin