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Abstract
Recent research has led to a better but as yet incomplete understanding of the complex
roles osteopontin plays in mammalian physiology. A soluble protein found in all body
fluids, it stimulates signal transduction pathways (via integrins and CD44 variants)
similar to those stimulated by components of the extracellular matrix. This appears
to promote the survival of cells exposed to potentially lethal insults such as ischemia/reperfusion
or physical/chemical trauma. OPN is chemotactic for many cell types including macrophages,
dendritic cells, and T cells; it enhances B lymphocyte immunoglobulin production and
proliferation. In inflammatory situations it stimulates both pro- and anti-inflammatory
processes, which on balance can be either beneficial or harmful depending on what
other inputs the cell is receiving. OPN influences cell-mediated immunity and has
been shown to have Th1-cytokine functions. OPN deficiency is linked to a reduced Th1
immune response in infectious diseases, autoimmunity and delayed type hypersensitivity.
OPN's role in the central nervous system and in stress responses has also emerged
as an important aspect related to its cytoprotective and immune functions. Evidence
suggests that either OPN or anti-OPN monoclonal antibodies (depending on the circumstances)
might be clinically useful in modulating OPN function. Manipulation of plasma OPN
levels may be useful in the treatment of autoimmune disease, cancer metastasis, osteoporosis
and some forms of stress.