title: Inhibition of Contractile Function in Human Joint Capsule Myofibroblasts by Targeting the TGF-β1 and PDGF Pathways.
abstract: BACKGROUND
  Contractile myofibroblasts (MFs) accumulate in the joint capsules of patients suffering from posttraumatic joint stiffness. MF activation is controlled by a complex local network of growth factors and cytokines, ending in the increased production of extracellular matrix components followed by soft tissue contracture. Despite the tremendous growth of knowledge in this field, inconsistencies remain in practice and prevention.
  
  
  RESULTS
  In this in vitro study, we isolated and cultured alpha-smooth muscle actin (α-SMA) positive human joint capsule MFs from biopsy specimens and investigated the effect of profibrotic and antifibrotic agents on MF function. Both TGF-β1 and PDGF significantly induced proliferation and increased extracellular matrix contraction in an established 3D collagen gel contraction model. Furthermore, both growth factors induced α-SMA and collagen type I gene expression in MFs. TGF-β1 down-regulated TGF-β1 and TGF-β receptor (R) 1 and receptor (R) 2 gene expression, while PDGF selectively down-regulated TGF-β receptor 2 gene expression. These effects were blocked by suramin. Interestingly, the anti-oxidant agent superoxide dismutase (SOD) blocked TGF-β1 induced proliferation and collagen gel contraction without modulating the gene expression of α-SMA, collagen type I, TGF-β1, TGF-β R1 and TGF-β R2.
  
  
  CONCLUSIONS
  Our results provide evidence that targeting the TGF-β1 and PDGF pathways in human joint capsule MFs affects their contractile function. TGF-β1 may modulate MF function in the joint capsule not only via the receptor signalling pathway but also by regulating the production of profibrotic reactive oxygen species (ROS). In particular, anti-oxidant agents could offer promising options in developing strategies for the prevention and treatment of posttraumatic joint stiffness in humans.
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Stefan G
authors.initials: SG
authors.lastname: Mattyasovszky
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Wollstädter
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Martin
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Ritz
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Baranowski
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Ossendorf
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Pol M
authors.initials: PM
authors.lastname: Rommens
authors.affiliation: Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Hofmann
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D005260:Female; D006801:Humans; D017746:Joint Capsule / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D013482:Superoxide Dismutase / Q000494:pharmacology*; D013498:Suramin / Q000494:pharmacology*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D000906:Antibodies; D000970:Antineoplastic Agents; D024042:Collagen Type I; D010982:Platelet-Derived Growth Factor; D018125:Receptors, Transforming Growth Factor beta; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D013498:Suramin; D013482:Superoxide Dismutase