PROLIFERATION AND DIFFERENTIATION OF OLIGODENDROCYTES IN CULTURE INDUCED BY A NEUROTROPHIC FACTOR PLEIOTROPHIN

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Pleiotrophin (PTN) is a novel neurotrophic factor with a molecular weight 18 kDa and a heparin-binding capacity. The expression of PTN is observed at a maximum level in the brain during myelination in the neonatal period. To investigate biological roles of PTN in proliferation and differentiation of oligodendrocytes (OL), a cell type responsible for myelination in the central nervous system (CNS), primary cultures of glial cells isolated from whole brains of the newbom rats were incubated for 72 h in the serum-free chemically-defined medium containing bromodeoxyuridine (BrdU), a marker for identification of cellular proliferation and a panel of neurotrophic and gliotrophic factors that include PTN,insulin-like growth factor I (IGF-I), basic fibroblast growth factor (bFGF), plalelet-derived growth factor-AA (PDGF) at a conentration of 50 ng/ml each, and their combinations, followed by analysis using double-labeling immunocytochemistry. A three-fold increase was induced in the number of O4^+BrdU^- immature OL by treatment with PTN and/or IGF-I,while a five-fold increase was induced in that of A2B5^+BrdU^+ OL progenitor cells after exposure to bFGF and/or PDGF.A three-fold increase was induced in the number of 01^+BrdU^- mature OL that constitute a very small population by treatment with IGF-I or bFGF plus PDGF but not with PTN.These results indicate that PTN is an important factor capable of inducing OL maturation during the CNS myelination.