Osteopontin is upregulated during in vivo demyelination and remyelination and enhances myelin formation in vitro.
We have used in vitro oligodendrocyte differentiation and the in vivo remyelination model, the cuprizone model, to identify genes regulating oligodendrocyte function and remyelination. One of the genes we identified, osteopontin (opn), is a secreted glycoprotein with cytokine-like, chemotactic, and anti-apoptotic properties that contains an Arg-Gly-Asp (RGD) cell adhesion motif-mediating interactions with several integrins. Both microglia and astrocytes in demyelinating brain regions of cuprizone-fed mice expressed OPN protein. Recombinant OPN protein produced in a baculovirus expression system induced proliferation of both the rat CG-4 and the mouse Oli-neu oligodendrocyte precursor (OLP)-like cell lines in a dose-dependent manner. In addition, recombinant OPN treatment stimulated both myelin basic protein (MBP) synthesis and myelin sheath formation in mixed cortical cultures from embryonic mouse brain, an in vitro primary culture model of myelination. Interestingly, myelinating mixed cultures prepared from OPN(-/-) mice contained significantly less MBP compared to wild-type cultures after 17 days in culture. We propose that in the central nervous system, OPN may act as a novel regulator of myelination and remyelination.
Selvaraju
Raghuram
R
Department of Immunology, Serono Pharmaceutical Research Institute, Ares-Serono International SA, Geneva, Switzerland.
Bernasconi
Lilia
L
Losberger
Christophe
C
Graber
Pierre
P
Kadi
Linda
L
Avellana-Adalid
Virginia
V
Picard-Riera
Nathalie
N
Baron Van Evercooren
Anne
A
Cirillo
Rocco
R
Kosco-Vilbois
Marie
M
Feger
Georg
G
Papoian
Ruben
R
Boschert
Ursula
U
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D018920:Coculture Techniques; D003471:Cuprizone; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009416:Nerve Regeneration / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism; D053495:Osteopontin; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012795:Sialoglycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D015854:Up-Regulation / Q000502:physiology*
D009185:Myelin Proteins; D011993:Recombinant Fusion Proteins; D012795:Sialoglycoproteins; C506896:Spp1 protein, mouse; C506897:Spp1 protein, rat; D053495:Osteopontin; D003471:Cuprizone