Matrix metalloproteinase-9 facilitates remyelination in part by processing the inhibitory NG2 proteoglycan.
Remyelination is a critical repair process that is initiated after a demyelinating insult. The failure to remyelinate contributes to neurological diseases such as multiple sclerosis. Here, we test the hypothesis that proteinase activity is required for the extensive remodeling of the extracellular matrix that occurs during remyelination. We show that mice lacking matrix metalloproteinase (MMP)-9 are impaired in myelin reformation after lysolecithin-induced demyelination. This deficiency may be explained at least in part by the failure to clear the accumulation of NG2, an inhibitory proteoglycan that retards the maturation and differentiation of oligodendrocytes that are needed for remyelination. These results emphasize for the first time that upregulation of MMP activity can be important for facilitating regeneration from some types of CNS injury.
Larsen
Peter H
PH
Neuroscience Research Group and the Department of Oncology, University of Calgary, Calgary, Alberta, Canada T2N 4N1.
Wells
Jennifer E
JE
Stallcup
William B
WB
Opdenakker
Ghislain
G
Yong
V Wee
VW
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007962:Leukocytes / Q000473:pathology; D008244:Lysophosphatidylcholines; D020780:Matrix Metalloproteinase 9 / Q000172:deficiency / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism*; D009836:Oligodendroglia / Q000473:pathology; D011499:Protein Processing, Post-Translational / Q000502:physiology*; D011509:Proteoglycans / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D008244:Lysophosphatidylcholines; D020780:Matrix Metalloproteinase 9; D011509:Proteoglycans; D000099216:Chondroitin Sulfate Proteoglycan 4