Osteopontin, A Novel Schwann Cell Molecule Regulated By Axonal Contact
Osteopontin (OPN) is a secreted phosphoglycoprotein, which interacts with the integrin on the cell surface. OPN was found originally in bone matrix and subsequently in kidney, placenta, blood vessels, adult rat brain and in a number of cell lines in response to inflammatory cytokines and growth factors. An elevated expression of OPN has been identified in a number of disease processes, including autoimmune disorders, and in a number of inflammatory reactions in peripheral organs with spatial and temporal association to macrophage migration and accumulation. Functionally, OPN has been implicated in cell attachment and chemotaxis, suggesting a functional role of the newly deposited matrix protein in cell-matrix interactions and remodelling. The aim of the present study was to investigate the distribution of osteopontin within the PNS, and in particular, 1) to determine the expression of osteopontin in rat Schwann cells cultured “in vitro,” 2) to define “in vivo” the spatial and temporal expression of osteopontin in the rat peripheral nerve in normal conditions and after crush injury, and 3) to study “in vivo” the possible correlation between OPN and neurofilament expression in human nerve biopsies from neuropathies of different origin. The results show that OPN is constitutively expressed in the PNS at the level of the Schwann cell. During Wallerian degeneration, only a transient increase of OPN mRNA was observed during the first 4 days after sciatic nerve crush. Similarly, OPN was expressed in Schwann cells in sural nerve biopsies which lack significant pathology. In chronic axonal polyneuropathy, as assessed by a decrease of neurofilament expression, OPN was dramatically reduced. In conclusion, these findings identify OPN as a novel Schwann cell antigen regulated by axonal contact. In contrast to other tissues, such as injured skin, ischemic heart and brain, where infiltrating macrophages express high levels of OPN during wound healing, OPN during Wallerian degeneration of the PNS appears to be downregulated.
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Document Type: Abstract
Affiliations: Istituto di Clinica Neurologica, Univ. Milano, IRCCS Ospedale Maggiore
Publication date: March 1, 2001