title: Isometric contraction of Dupuytren's myofibroblasts is inhibited by blocking intercellular junctions.
abstract: Myofibroblasts (MFs) are responsible for both physiological wound and scar contraction. However, it is not known whether these cells act individually to contract the surrounding matrix or whether they behave in a coordinated manner. Therefore, we studied intercellular junctions of primary human MFs derived from patients with Dupuytren's disease, a fibrotic disorder of the dermis and subdermal tissues of the palm. The cells were maintained in anchored three-dimensional collagen lattices to closely mimic conditions in vivo. We found that selective blockade of adherens, mechanosensitive, or gap junctions effectively inhibited contraction of the collagen matrices and downregulated the MF phenotype. Our data indicate that MFs in part function as a coordinated cellular syncytium, and disruption of intercellular communication may provide a therapeutic target in diseases characterized by an overabundance of these contractile cells.
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK; Department of Plastic and Reconstructive Surgery, Erasmus Medical Centre, Rotterdam, The Netherlands.
authors: Jennifer S N
authors: JSN
authors: Verhoekx
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors: Liaquat S
authors: LS
authors: Verjee
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors: David
authors: D
authors: Izadi
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors: James K K
authors: JKK
authors: Chan
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors: Vicky
authors: V
authors: Nicolaidou
authors: Department of Plastic Surgery, St John's Hospital, Livingstone, UK.
authors: Dominique
authors: D
authors: Davidson
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK.
authors: Kim S
authors: KS
authors: Midwood
authors: Kennedy Institute of Rheumatology, University of Oxford, London, UK. Electronic address: jagdeep.nanchahal@kennedy.ox.ac.uk.
authors: Jagdeep
authors: J
authors: Nanchahal
mesh_terms: D015820:Cadherins / Q000378:metabolism; D002450:Cell Communication; D002478:Cells, Cultured; D003094:Collagen / Q000737:chemistry; D004387:Dupuytren Contracture / Q000503:physiopathology*; D005347:Fibroblasts / Q000166:cytology; D017629:Gap Junctions / Q000378:metabolism; D015726:Giant Cells / Q000378:metabolism; D006801:Humans; D007365:Intercellular Junctions / Q000502:physiology*; D007537:Isometric Contraction; D008856:Microscopy, Fluorescence; D058628:Myofibroblasts / Q000473:pathology*; D010641:Phenotype; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000166:cytology
chemical_list: D015820:Cadherins; D034741:RNA, Small Interfering; C086960:osteoblast cadherin; D003094:Collagen