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Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis

The aim of the present study was to investigate the expression of Fas in periarticular tenocytes of patients with osteoarthritis (OA) and to study their susceptibility to Fas ligand-mediated apoptosis. Tendon samples were obtained from the quadriceps femoris muscle of patients with knee OA and used...

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Autores principales: Machner, Andreas, Baier, Anja, Wille, Aline, Drynda, Susanne, Pap, Géza, Drynda, Andreas, Mawrin, Christian, Bühling, Frank, Gay, Steffen, Neumann, Wolfram, Pap, Thomas
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193726/
https://www.ncbi.nlm.nih.gov/pubmed/12932288
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author Machner, Andreas
Baier, Anja
Wille, Aline
Drynda, Susanne
Pap, Géza
Drynda, Andreas
Mawrin, Christian
Bühling, Frank
Gay, Steffen
Neumann, Wolfram
Pap, Thomas
author_facet Machner, Andreas
Baier, Anja
Wille, Aline
Drynda, Susanne
Pap, Géza
Drynda, Andreas
Mawrin, Christian
Bühling, Frank
Gay, Steffen
Neumann, Wolfram
Pap, Thomas
author_sort Machner, Andreas
collection PubMed
description The aim of the present study was to investigate the expression of Fas in periarticular tenocytes of patients with osteoarthritis (OA) and to study their susceptibility to Fas ligand-mediated apoptosis. Tendon samples were obtained from the quadriceps femoris muscle of patients with knee OA and used for histological evaluation, for immunohistochemical detection of Fas, and to establish tenocyte cultures. The expression of Fas mRNA was determined by quantitative PCR. Levels of soluble Fas and soluble tumour necrosis factor (TNF) receptor I were measured using ELISA. Apoptosis was induced with recombinant human Fas ligand and measured by a histone fragmentation assay and flow cytometry. The effects of TNF-α were studied by stimulation with TNF-α alone or 24 hours before the induction of apoptosis. Tendon samples from non-OA patients were used as controls. Histological evaluation revealed degenerative changes in the tendons of all OA patients but not in the controls. Fas was detected by immunohistochemistry in all specimens, but quantitative PCR revealed significantly higher levels of Fas mRNA in OA tenocytes. In contrast, lower levels of soluble Fas were found in OA tenocytes by ELISA. OA tenocytes were significantly more susceptible to Fas ligand induced apoptosis than were control cells. TNF-α reduced the Fas ligand induced apoptosis in OA tenocytes but had no effects on control tenocytes. These data suggest that knee OA is associated with higher susceptibility of periarticular tenocytes to Fas ligand induced apoptosis because of higher expression of Fas but lower levels of apoptosis-inhibiting soluble Fas. These changes may contribute to decreased cellularity in degenerative tendons and promote their rupturing. The antiapoptotic effects of TNF-α in OA tenocytes most likely reflect regenerative attempts and must be taken into account when anti-TNF strategies are considered for OA.
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spelling pubmed-1937262003-09-15 Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis Machner, Andreas Baier, Anja Wille, Aline Drynda, Susanne Pap, Géza Drynda, Andreas Mawrin, Christian Bühling, Frank Gay, Steffen Neumann, Wolfram Pap, Thomas Arthritis Res Ther Research Article The aim of the present study was to investigate the expression of Fas in periarticular tenocytes of patients with osteoarthritis (OA) and to study their susceptibility to Fas ligand-mediated apoptosis. Tendon samples were obtained from the quadriceps femoris muscle of patients with knee OA and used for histological evaluation, for immunohistochemical detection of Fas, and to establish tenocyte cultures. The expression of Fas mRNA was determined by quantitative PCR. Levels of soluble Fas and soluble tumour necrosis factor (TNF) receptor I were measured using ELISA. Apoptosis was induced with recombinant human Fas ligand and measured by a histone fragmentation assay and flow cytometry. The effects of TNF-α were studied by stimulation with TNF-α alone or 24 hours before the induction of apoptosis. Tendon samples from non-OA patients were used as controls. Histological evaluation revealed degenerative changes in the tendons of all OA patients but not in the controls. Fas was detected by immunohistochemistry in all specimens, but quantitative PCR revealed significantly higher levels of Fas mRNA in OA tenocytes. In contrast, lower levels of soluble Fas were found in OA tenocytes by ELISA. OA tenocytes were significantly more susceptible to Fas ligand induced apoptosis than were control cells. TNF-α reduced the Fas ligand induced apoptosis in OA tenocytes but had no effects on control tenocytes. These data suggest that knee OA is associated with higher susceptibility of periarticular tenocytes to Fas ligand induced apoptosis because of higher expression of Fas but lower levels of apoptosis-inhibiting soluble Fas. These changes may contribute to decreased cellularity in degenerative tendons and promote their rupturing. The antiapoptotic effects of TNF-α in OA tenocytes most likely reflect regenerative attempts and must be taken into account when anti-TNF strategies are considered for OA. BioMed Central 2003 2003-06-30 /pmc/articles/PMC193726/ /pubmed/12932288 Text en Copyright © 2003 Machner et al., licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
spellingShingle Research Article
Machner, Andreas
Baier, Anja
Wille, Aline
Drynda, Susanne
Pap, Géza
Drynda, Andreas
Mawrin, Christian
Bühling, Frank
Gay, Steffen
Neumann, Wolfram
Pap, Thomas
Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title_full Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title_fullStr Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title_full_unstemmed Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title_short Higher susceptibility to Fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
title_sort higher susceptibility to fas ligand induced apoptosis and altered modulation of cell death by tumor necrosis factor-α in periarticular tenocytes from patients with knee joint osteoarthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC193726/
https://www.ncbi.nlm.nih.gov/pubmed/12932288
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