Effects of Transforming Growth Factor-β and Platelet-Derived Growth Factor on Oligodendrocyte Precursors: Insights Gained from a Neuronal Cell Line


Address correspondence and reprint requests to Dr. M. Rodriguez at Department of Immunology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, U.S.A.


Abstract: Conditioned medium derived from a rat central nervous system neuronal cell line B104 (B104 CM) was shown previously to contain uncharacterized potent mitogen(s) for oligodendrocyte/type-2 astrocyte (O-2A) progenitor cells. In this study, we demonstrated that B104 cells produce and secrete platelet-derived growth factor (PDGF)-AA homodimer, but not PDGF-B chain. B104 cells did not express other known potent mitogens for O-2A progenitor cells, including fibroblast growth factor-2 and neurotrophin-3. Unexpectedly, B104 cells also expressed transcripts of transforming growth factor-β1 (TGF-β1) and -β2 (TGF-β2), which are known to regulate O-2A progenitor cell differentiation and proliferation, and secreted exclusively the 25-kDa active forms of TGF-β1 and TGF-β2. Neutralization of B104 CM with anti-PDGF-AA antibody decreased proliferation of O-2A progenitor cells, whereas neutralization with anti-TGF-β antibodies had no effect. The combination of PDGF and TGF-β on proliferation was not equivalent to the effect of B104 CM, indicating the possibility of an unidentified growth factor. B104 CM maintained a high expression of PDGF-α receptor in oligodendrocytes. The observation that both a stimulatory factor (PDGF-AA) and a regulatory factor (TGF-β) for O-2A progenitor cell proliferation and differentiation are produced from a single neuronal cell line emphasizes the potential critical interaction between neurons and O-2A progenitor cells in myelination and possibly in remyelination.

Abbreviations used: BrdU, bromodeoxyuridine; Cdk, cyclin-dependent kinase; CM, conditioned medium; DMEM, Dulbecco's modified Eagle's medium; FCS, fetal calf serum; FGF, fibroblast growth factor; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; GFAP, glial fibrillary acidic protein; NGS, normal goat serum; NT-3, neurotrophin-3; O-2A, oligodendrocyte/type-2 astrocyte; PBS, phosphate-buffered saline; PDGF, platelet-derived growth factor; RT-PCR, reverse transcription and polymerase chain reaction; TGF-β, transforming growth factor-β.