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Inhibiting bone morphogenetic protein 4 Type I receptor signaling promotes remyelination by potentiating oligodendrocyte differentiation
Citation
Govier-Cole, AE and Wood, RJ and Fletcher, JL and Gonsalvez, DG and Merlo, D and Cate, HS and Murray, SS and Xiao, J, Inhibiting bone morphogenetic protein 4 Type I receptor signaling promotes remyelination by potentiating oligodendrocyte differentiation, eNeuro, 6, (2) pp. 1-22. ISSN 2373-2822 (2021) [Refereed Article]
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Copyright Statement
Copyright © 2019 Govier-Cole et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license, (https://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
DOI: doi:10.1523/ENEURO.0399-18.2019
Abstract
Blocking inhibitory factors within CNS demyelinating lesions is regarded as a promising strategy to promote remyelination. Bone morphogenetic protein 4 (BMP4) is an inhibitory factor present in demyelinating lesions. Noggin, an endogenous antagonist to BMP, has previously been shown to increase the number of oligodendrocytes and promote remyelination in vivo. However, it remains unclear how BMP4 signaling inhibits remyelination. Here we investigated the downstream signaling pathway that mediates the inhibitory effect that BMP4 exerts upon remyelination through pharmacological and transgenic approaches. Using the cuprizone mouse model of central demyelination, we demonstrate that selectively blocking BMP4 signaling via the pharmacological inhibitor LDN-193189 significantly promotes oligodendroglial differentiation and the extent of remyelination in vivo This was accompanied by the downregulation of transcriptional targets that suppress oligodendrocyte differentiation. Further, selective deletion of BMP receptor type IA (BMPRIA) within primary mouse oligodendrocyte progenitor cells (OPCs) significantly enhanced their differentiation and subsequent myelination in vitro Together, the results of this study identify that BMP4 signals via BMPRIA within OPCs to inhibit oligodendroglial differentiation and their capacity to myelinate axons, and suggest that blocking the BMP4/BMPRIA pathway in OPCs is a promising strategy to promote CNS remyelination.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | oligodendrocyte, myelin, multiple sclerosis, demyelinating disease, animal model |
| Research Division: | Biomedical and Clinical Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurology and neuromuscular diseases |
| Objective Division: | Expanding Knowledge |
| Objective Group: | Expanding knowledge |
| Objective Field: | Expanding knowledge in the biomedical and clinical sciences |
| UTAS Author: | Fletcher, JL (Dr Jessica Fletcher) |
| ID Code: | 147220 |
| Year Published: | 2021 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2021-10-19 |
| Last Modified: | 2021-11-03 |
| Downloads: | 5 View Download Statistics |
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