title: MT1-MMP controls human mesenchymal stem cell trafficking and differentiation.
abstract: Human mesenchymal stem cells (hMSCs) localized to bone marrow, nonhematopoietic organs, as well as perivascular niches are postulated to traffic through type I collagen-rich stromal tissues to first infiltrate sites of tissue damage, inflammation, or neoplasia and then differentiate. Nevertheless, the molecular mechanisms supporting the ability of hMSCs to remodel 3-dimensional (3D) collagenous barriers during trafficking or differentiation remain undefined. Herein, we demonstrate that hMSCs degrade and penetrate type I collagen networks in tandem with the expression of a 5-member set of collagenolytic matrix metalloproteinases (MMPs). Specific silencing of each of these proteases reveals that only a single membrane-tethered metalloenzyme, termed MT1-MMP, plays a required role in hMSC-mediated collagenolysis, 3D invasion, and intravasation. Further, once confined within type I collagen-rich tissue, MT1-MMP also controls hMSC differentiation in a 3D-specific fashion. Together, these data demonstrate that hMSC invasion and differentiation programs fall under the control of the pericellular collagenase, MT1-MMP.
authors.affiliation: College of Pharmacy, Harbin Medical University, Harbin, China.
authors.forename: Changlian
authors.initials: C
authors.lastname: Lu
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Li
authors.forename: Yuexian
authors.initials: Y
authors.lastname: Hu
authors.forename: R Grant
authors.initials: RG
authors.lastname: Rowe
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Weiss
mesh_terms: D002454:Cell Differentiation / Q000502:physiology*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D024042:Collagen Type I / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D020868:Gene Silencing; D006801:Humans; D053511:Matrix Metalloproteinase 14 / Q000096:biosynthesis*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000201:enzymology*
chemical_list: D024042:Collagen Type I; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14