MT1-MMP controls human mesenchymal stem cell trafficking and differentiation.
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.
Lu
Changlian
C
College of Pharmacy, Harbin Medical University, Harbin, China.
Li
Xiao-Yan
XY
Hu
Yuexian
Y
Rowe
R Grant
RG
Weiss
Stephen J
SJ
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*
D024042:Collagen Type I; C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14