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As MS progresses, remyelination increasingly fails, leaving neuronal axons vulnerable to degeneration and resulting in permanent neurological disability. In chronic MS lesions, the aberrant accumulation of extracellular matrix (ECM) molecules, including fibronectin and hyaluronan, impairs oligodendrocyte progenitor cell differentiation, contributing to remyelination failure. Removing inhibitory ECM is therefore a therapeutic target to stimulate remyelination in MS. Intriguingly, the expression of the fibronectin\u2010degrading enzyme matrix metalloproteinase 7 (MMP7) is decreased in chronic MS lesions compared to control white matter. Therefore, we examined the role of MMP7 upon cuprizone\u2010induced demyelination, hypothesizing that the lack of MMP7 would lead to impaired breakdown of its ECM substrates, including fibronectin, and diminished remyelination. Unexpectedly, remyelination proceeded efficiently in the absence of MMP7. In the remyelination phase, the lack of MMP7 did not lead to the accumulation of fibronectin or of laminin, another MMP7 substrate. Moreover, in the setting of chronic demyelination, levels of fibronectin were actually lower in MMP7<jats:sup>\u2212\/\u2212<\/jats:sup> mice, while levels of hyaluronan, which is not a known MMP7 substrate, were also lower. Overall, these results indicate that MMP7 is not essential for remyelination in the cuprizone model and point to an unexpected complexity in how MMP7 deficiency influences fibronectin and hyaluronan levels in chronic demyelination.<\/jats:p>","DOI":"10.1002\/glia.70005","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T06:22:56Z","timestamp":1741760576000},"page":"1288-1306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Unexpected Remyelination in the Absence of Matrix Metalloproteinase 7"],"prefix":"10.1002","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9014-0503","authenticated-orcid":false,"given":"Rianne P.","family":"Gorter","sequence":"first","affiliation":[{"name":"Department of Biomedical Sciences University of Groningen, University Medical Center Groningen  Groningen the Netherlands"},{"name":"Queen Mary University of London MS Center Noord 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