title: Matrix metalloproteinase 14 is required for fibrous tissue expansion.
abstract: Type I collagen-containing fibrils are major structural components of the extracellular matrix of vertebrate tissues, especially tendon, but how they are formed is not fully understood. MMP14 is a potent pericellular collagenase that can cleave type I collagen in vitro. In this study, we show that tendon development is arrested in Scleraxis-Cre::Mmp14 lox/lox mice that are unable to release collagen fibrils from plasma membrane fibripositors. In contrast to its role in collagen turnover in adult tissue, MMP14 promotes embryonic tissue formation by releasing collagen fibrils from the cell surface. Notably, the tendons grow to normal size and collagen fibril release from fibripositors occurs in Col-r/r mice that have a mutated collagen-I that is uncleavable by MMPs. Furthermore, fibronectin (not collagen-I) accumulates in the tendons of Mmp14-null mice. We propose a model for cell-regulated collagen fibril assembly during tendon development in which MMP14 cleaves a molecular bridge tethering collagen fibrils to the plasma membrane of fibripositors.
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Susan H
authors.initials: SH
authors.lastname: Taylor
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Ching-Yan Chloé
authors.initials: CY
authors.lastname: Yeung
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Nicholas S
authors.identifier: http://orcid.org/0000-0001-8394-3060
authors.initials: NS
authors.lastname: Kalson
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Yinhui
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Dermatology, Center for Molecular Medicine, University of Cologne, Cologne, Germany.
authors.forename: Paola
authors.initials: P
authors.lastname: Zigrino
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Tobias
authors.initials: T
authors.lastname: Starborg
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Stacey
authors.initials: S
authors.lastname: Warwood
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: David F
authors.initials: DF
authors.lastname: Holmes
authors.affiliation: Department of Musculoskeletal Biology, Institute of Ageing and Chronic Disease, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, United Kingdom.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Canty-Laird
authors.affiliation: Department of Dermatology, Center for Molecular Medicine, University of Cologne, Cologne, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Mauch
authors.affiliation: Wellcome Trust Centre for Cell-Matrix Research, Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom.
authors.forename: Karl E
authors.identifier: http://orcid.org/0000-0003-4977-4683
authors.initials: KE
authors.lastname: Kadler
mesh_terms: D000818:Animals; D024042:Collagen Type I / Q000378:metabolism*; D005353:Fibronectins / Q000378:metabolism; D017353:Gene Deletion; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D013710:Tendons / Q000254:growth & development* / Q000378:metabolism
chemical_list: D024042:Collagen Type I; D005353:Fibronectins; D053511:Matrix Metalloproteinase 14
keywords: MT1-MMP; cell biology; chicken; collagen; developmental biology; electron microscope; fibripositor; fibronectin; mouse; periostin; stem cells