Your browser doesn't support javascript.
loading
Inhibition of Contractile Function in Human Joint Capsule Myofibroblasts by Targeting the TGF-ß1 and PDGF Pathways.
Mattyasovszky, Stefan G; Wollstädter, Jochen; Martin, Anne; Ritz, Ulrike; Baranowski, Andreas; Ossendorf, Christian; Rommens, Pol M; Hofmann, Alexander.
Afiliación
  • Mattyasovszky SG; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Wollstädter J; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Martin A; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Ritz U; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Baranowski A; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Ossendorf C; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Rommens PM; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
  • Hofmann A; Department of Orthopaedics and Traumatology, University Medical Centre of the Johannes Gutenberg-University of Mainz, Mainz, Germany.
PLoS One ; 11(1): e0145948, 2016.
Article en En | MEDLINE | ID: mdl-26730954
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. METHODS AND

FINDINGS:

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-ß1 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-ß1 down-regulated TGF-ß1 and TGF-ß receptor (R) 1 and receptor (R) 2 gene expression, while PDGF selectively down-regulated TGF-ß receptor 2 gene expression. These effects were blocked by suramin. Interestingly, the anti-oxidant agent superoxide dismutase (SOD) blocked TGF-ß1 induced proliferation and collagen gel contraction without modulating the gene expression of α-SMA, collagen type I, TGF-ß1, TGF-ß R1 and TGF-ß R2.

CONCLUSIONS:

Our results provide evidence that targeting the TGF-ß1 and PDGF pathways in human joint capsule MFs affects their contractile function. TGF-ß1 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.
Asunto(s)

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Superóxido Dismutasa / Suramina / Factor de Crecimiento Derivado de Plaquetas / Cápsula Articular / Factor de Crecimiento Transformador beta1 / Miofibroblastos / Anticuerpos Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Alemania

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Superóxido Dismutasa / Suramina / Factor de Crecimiento Derivado de Plaquetas / Cápsula Articular / Factor de Crecimiento Transformador beta1 / Miofibroblastos / Anticuerpos Tipo de estudio: Prognostic_studies Límite: Adult / Aged / Aged80 / Female / Humans / Male / Middle aged Idioma: En Revista: PLoS One Asunto de la revista: CIENCIA / MEDICINA Año: 2016 Tipo del documento: Article País de afiliación: Alemania