Effects of transforming growth factor-beta and platelet-derived growth factor on oligodendrocyte precursors: insights gained from a neuronal cell line.
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-beta1 (TGF-beta1) and -beta2 (TGF-beta2), which are known to regulate O-2A progenitor cell differentiation and proliferation, and secreted exclusively the 25-kDa active forms of TGF-beta1 and TGF-beta2. Neutralization of B104 CM with anti-PDGF-AA antibody decreased proliferation of O-2A progenitor cells, whereas neutralization with anti-TGF-beta antibodies had no effect. The combination of PDGF and TGF-beta 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-alpha receptor in oligodendrocytes. The observation that both a stimulatory factor (PDGF-AA) and a regulatory factor (TGF-beta) 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.
Asakura
K
K
Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, U.S.A.
Hunter
S F
SF
Rodriguez
M
M
D000818:Animals; D000831:Animals, Newborn; D000963:Antimetabolites / Q000378:metabolism / Q000494:pharmacology; D000077214:Becaplermin; D001973:Bromodeoxyuridine / Q000378:metabolism / Q000494:pharmacology; D002455:Cell Division / Q000502:physiology; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology; D019281:Dimerization; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism; D020933:Neurotrophin 3; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000235:genetics* / Q000378:metabolism; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000235:genetics* / Q000378:metabolism; D014316:Tritium
D000963:Antimetabolites; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; C075278:platelet-derived growth factor A; D014316:Tritium; D016222:Fibroblast Growth Factor 2; D000077214:Becaplermin; D001973:Bromodeoxyuridine; D013936:Thymidine