gms | German Medical Science

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017)

24.10. - 27.10.2017, Berlin

TNF disturbs anti-inflammatory function of catecholamine producing synovial cells in osteoarthritis and rheumatoid arthritis by inhibiting tyrosine hydroxylase

Meeting Abstract

Suche in Medline nach

  • presenting/speaker Zsuzsa Jenei-Lanzl - Orthopedic University Hospital Friedrichsheim gGmbh, Dr. Rolf M. Schwiete Research Unit, Frankfurt, Germany
  • Markus Herrmann - Department of Internal Medicine, Lab of Exp. Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg, Regensburg, Germany
  • Rainer H. Straub - Department of Internal Medicine, Lab of Exp. Rheumatology and Neuroendocrine Immunology, University Hospital Regensburg, Regensburg, Germany

Deutscher Kongress für Orthopädie und Unfallchirurgie (DKOU 2017). Berlin, 24.-27.10.2017. Düsseldorf: German Medical Science GMS Publishing House; 2017. DocPO12-665

doi: 10.3205/17dkou618, urn:nbn:de:0183-17dkou6185

Veröffentlicht: 23. Oktober 2017

© 2017 Jenei-Lanzl et al.
Dieser Artikel ist ein Open-Access-Artikel und steht unter den Lizenzbedingungen der Creative Commons Attribution 4.0 License (Namensnennung). Lizenz-Angaben siehe http://creativecommons.org/licenses/by/4.0/.


Gliederung

Text

Objectives: Recently, synovial cells in chronic inflammation have been shown to express tyrosine-hydroxylase (TH) and to release catecholamines, possibly, trying to compensate the function of repelled sympathetic nerve fibers. These TH+ cells mediate anti-inflammatory effects in vitro and in experimental arthritis in vivo [1]. The pro-inflammatory cytokine TNF is known to be toxic to catecholaminergic neurons in Parkinson's disease (PD) [2]. The aim of this study was to analyze whether TNF exhibits similar inhibitory effects on TH+ cells derived from chronic inflamed synovium in osteoarthritis (OA) and rheumatoid arthritis (RA).

Methods: Human mixed synovial cells were isolated from RA and OA patients and "induced TH+ cells" (iTH+) were generated from human mesenchymal stem cells (MSC) derived from synovial adipose tissue as described previously.a Cells were cultured under hypoxia (1% O2), because the microenvironment of inflamed joints is hypoxic. TNF and etanercept (soluble TNF receptor 2) were administered in different concentrations and combinations. In addition, iTH were treated with synovial fluid of RA patients during dopaminergic differentiation in order to mimic effects on newly appearing TH+ cells. Expression of TH was analyzed by immunofluorescence and TH activity was measured by a newly established enzyme activity assay. Catecholamines were quantified via HPLC and the quality of catecholaminergic differentiation was investigated staining VMAT2, Nurr1, and beta-III tubulin as markers.

Results and Conclusion: In mixed synovial cell culture, no significant effects of TNF on TH activity and catecholamine synthesis were observed. TH staining of TNF-treated iTH+ cells was weaker, the TH activity and the amount of produced catecholamines was lower compared to untreated controls in both OA and RA. Similarly, expression of VMAT2, Nurr1, and beta-III tubulin decreased after TNF-treatment in iTH+ cells. The effects of TNF were reversed by etanercept in RA/OA iTH+ cell cultures. Exposure to synovial fluid of RA patients showed similar inhibitory effects on iTH+ cells.

This study shows that TNF, present in high concentrations in synovial fluid, unfolds its pro-inflammatory effects also by inhibition of TH expression and activity of iTH+ synovial cells leading to the decrease of anti-inflammatory catecholamines. This might be a reason why newly appearing TH+ cells in the synovium are not able to unfold their anti-inflammatory effects in RA. This phenomenon was not confirmed observed in mixed synovial cell culture, possibly, due to preceding TNF-priming in the inflamed joint.


References

1.
Jenei-Lanzl Z, Capellino S, Kees F, Fleck M, Lowin T, Straub RH. Anti-inflammatory effects of cell-based therapy with tyrosine hydroxylase-positive catecholaminergic cells in experimental arthritis. Ann Rheum Dis. 2015 Feb;74(2):444-51. DOI: 10.1136/annrheumdis-2013-203925 Externer Link
2.
McCoy MK, Martinez TN, Ruhn KA, Szymkowski DE, Smith CG, Botterman BR, Tansey KE, Tansey MG. Blocking soluble tumor necrosis factor signaling with dominant-negative tumor necrosis factor inhibitor attenuates loss of dopaminergic neurons in models of Parkinson's disease. J Neurosci. 2006 Sep;26(37):9365-75. DOI: 10.1523/JNEUROSCI.1504-06.2006 Externer Link