Authors:	Mattyasovszky, Stefan Wollstädter, Jochen Martin, Anne Ritz, Ulrike Baranowski, Andreas Ossendorf, Christian Rommens, Pol Maria Hofmann, Alexander
Title:	Inhibition of contractile function in human joint capsule myofibroblasts by targeting the TGF-β1 and PDGF pathways
Online publication date:	13-Oct-2022
Year of first publication:	2016
Language:	english
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-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.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-7968
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	PLoS one 11 1
Pages or article number:	e0145948
Publisher:	PLoS
Publisher place:	Lawrence, Kan.
Issue date:	2016
ISSN:	1932-6203
Publisher URL:	http://dx.doi.org/10.1371/journal.pone.0145948
Publisher DOI:	10.1371/journal.pone.0145948
Appears in collections:	DFG-OA-Publizieren (2012 - 2017)