Osteopontin is extensively expressed by macrophages following CNS demyelination but has a redundant role in remyelination.
Osteopontin (OPN) is a key immunoregulator in the autoimmune-mediated demyelinating disease multiple sclerosis. OPN may also play a role in the remyelination since it is 1) a ligand for alpha V integrins, several of which regulate the properties of the oligodendrocyte precursor cells (OPCs) primarily responsible for remyelination, and 2) enhances myelin membrane formation in OPC lines. Here we show that OPN is expressed at high levels during remyelination of toxin-induced demyelination. The increased expression is due to mRNA expression in macrophages and follows differences in macrophage responses to demyelination in young and old adult animals. To identify the role of OPN in remyelination focal demyelination was induced in wild-type and OPN(-/-) mice. There was no difference in the rate of remyelination between the two groups indicating that OPN is not a critical component of remyelination.
Department of Veterinary Medicine and Cambridge Centre for Brain Repair, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK.
Chao
C
Zhao
Stephen P J
SP
Fancy
Charles
C
ffrench-Constant
Robin J M
RJ
Franklin
D000367:Age Factors; D000375:Aging / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002490:Central Nervous System / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003711:Demyelinating Diseases / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009416:Nerve Regeneration / Q000235:genetics*; D009836:Oligodendroglia / Q000378:metabolism; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000378:metabolism
D012333:RNA, Messenger; C506896:Spp1 protein, mouse; D053495:Osteopontin