title: Osteopontin, a macrophage-derived matricellular glycoprotein, inhibits axon outgrowth.
abstract: Transected axons can regenerate beyond the site of injury in the peripheral but not in the central nervous system (CNS). Increasing evidence implicates inflammatory processes as modulators of axon regeneration after injury. In this study, we addressed a possible role of the matricellular glycoprotein osteopontin (OPN) using crush lesions of the optic and sciatic nerve as models of central and peripheral axotomy, respectively. OPN was strongly expressed by macrophages at the crush site in the optic but not sciatic nerve, indicating fundamental differences in the molecular programming of macrophages in both systems. Functionally, OPN exerted potent growth-inhibitory effects in an in vitro assay of axon outgrowth. Therefore, OPN expression by lesion-associated macrophages may contribute to the nonpermissive nature of the adult CNS preventing axonal regeneration following injury.
authors.affiliation: Department of Neurology, Heinrich-Heine-University,Düsseldorf, Germany.
authors.forename: Patrick
authors.initials: P
authors.lastname: Küry
authors.forename: Philipp
authors.initials: P
authors.lastname: Zickler
authors.forename: Guido
authors.initials: G
authors.lastname: Stoll
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Hartung
authors.forename: Sebastian
authors.initials: S
authors.lastname: Jander
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D002448:Cell Adhesion; D016207:Cytokines / Q000502:physiology; D005727:Ganglia, Spinal / Q000196:embryology / Q000648:ultrastructure; D015870:Gene Expression; D007150:Immunohistochemistry; D007700:Kinetics; D008264:Macrophages / Q000737:chemistry / Q000378:metabolism*; D009409:Nerve Crush; D009416:Nerve Regeneration / Q000187:drug effects; D009900:Optic Nerve / Q000737:chemistry / Q000648:ultrastructure; D053495:Osteopontin; D016133:Polymerase Chain Reaction; D051381:Rats; D012584:Sciatic Nerve / Q000737:chemistry / Q000648:ultrastructure; D012795:Sialoglycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*
chemical_list: D016207:Cytokines; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D053495:Osteopontin