Osteopontin information and research
Osteopontin produced by cells of the immune system, epithelial tissue, smooth muscle cells, osteoblasts and tumor cells has been implicated in various pathophysiological functions such as cell binding, spreading and migration, and tumor metastasis.
Control of osteopontin signaling and function by
post-translational phosphorylation and protein folding.
J Cell Biochem. 2007 Nov 1; Kazanecki CC, Uzwiak DJ, Denhardt DT. Division of
Life Sciences, Rutgers University, Piscataway, New Jersey, USA.
Osteopontin plays roles in a variety of cellular processes from
bone resorption
and extracellular matrix (ECM) remodeling to immune cell activation and
inhibition of apoptosis. Because it binds receptors (integrins, CD44 variants)
typically engaged by ECM molecules, Osteopontin acts as a "soluble" ECM
molecule. A persistent theme throughout the characterization of how Osteopontin
functions has been the importance of phosphorylation. The source of the
Osteopontin used in specific experiments and the location of modified sites is
an increasingly important consideration for Osteopontin research. We review
briefly some of the ways Osteopontin impacts on the biology of mammalian systems
with an emphasis on the importance of serine phosphorylation in modulating its
signaling ability. We describe experiments that support the hypothesis that
differences in the post-translational phosphorylation of Osteopontin expressed
by different cell types regulate how it impacts on target cells. Analyses of
Osteopontin potential secondary structure reveal a possible beta-sheet
conformation that offers an interpretation of certain experimental observations,
specifically the effect of thrombin cleavage; it is consistent with an
interaction between the C-terminal region of the protein and the central
integrin-binding RGD sequence.
Role of osteopontin in regulating hepatic inflammatory
responses and toxic liver injury.
Expert Opin Drug Metab Toxicol. 2007 Aug; Ramaiah SK, Rittling S. Texas A & M
University, Department of Pathobiology, College of Veterinary Medicine, MS-4467,
College Station, TX 77843-4467, USA.
Osteopontin is
known to bind to integrins expressed on macrophages through the
arginine-glycine-aspartic acid (RGD) motif and promote migration of cells
resulting in granuloma. In the liver, it has been reported that hepatic Kupffer
cells secrete Osteopontin
facilitating macrophage infiltration in necrotic areas
following carbon tetrachloride liver toxicity. Recent work has underlined the
importance of Osteopontin
as a pivotal cytokine/chemokine in the generated hepatic
neutrophil response during early phase alcoholic liver injury. Increased
hepatobiliary OPN expression correlated well with higher neutrophil infiltration
in a rat model of alcoholic steatohepatitis. In the same model of alcoholic
steatohepatitis, higher hepatic expression of Osteopontin
in females was attributed to the higher neutrophil
infiltration and consequent higher female sensitivity to liver damage.
Osteopontin as a
potential biomarker for inflammatory liver disease has also been recently
assessed. This review will focus on studies demonstrating the role of
Osteopontin in
mediating hepatic inflammation (neutrophils, monocytes/macrophages and
lymphocytes) and the ensuing liver toxicity.
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