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Profiling the secretion of soluble mediators by end stage osteoarthritis synovial tissue explants reveals a reduced responsiveness to an inflammatory trigger.

Gierman LM, van El B, van der Ham F, Koudijs A, Stoop R, Verheijen JH, Kloppenburg M, van Osch GJ, Stojanovic-Susulic V, Huizinga TW, Zuurmond AM - PLoS ONE (2013)

Bottom Line: No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients.The effects could be the result of prolonged exposure to an inflammatory environment in OA development.

View Article: PubMed Central - PubMed

Affiliation: TNO, Leiden, The Netherlands.

ABSTRACT

Objective: Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration.

Methods: Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined.

Results: Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p<0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.

Conclusions: Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.

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Related in: MedlinePlus

Soluble mediator secretion by non-stimulated and stimulated synovial tissue explants (STEs) from normal and OA donors.Graphs demonstrate the absolute levels of all soluble mediators, which were significantly (p<0.01) different between A. non-stimulated (black bars) and IL-1α-stimulated (white bars) normal STEs and B. non-stimulated (grey bars) and IL-1α-stimulated (white bars) OA STEs. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.
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pone-0062634-g002: Soluble mediator secretion by non-stimulated and stimulated synovial tissue explants (STEs) from normal and OA donors.Graphs demonstrate the absolute levels of all soluble mediators, which were significantly (p<0.01) different between A. non-stimulated (black bars) and IL-1α-stimulated (white bars) normal STEs and B. non-stimulated (grey bars) and IL-1α-stimulated (white bars) OA STEs. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.

Mentions: To assess the response to an inflammatory trigger of STEs from normal and OA donors, soluble mediator excretion levels were analyzed in both the non-stimulated and the IL-1α-stimulated condition. For normal STEs, 16 mediators increased significantly (p<0.01) after stimulation with IL-1α (Figure 2A). Unexpectedly, the STEs obtained from OA donors secreted only 3 mediators at a significantly different level after IL-1α stimulation (Figure 2B). An overview of all measured mediators in these supernatants can be consulted in table S1.


Profiling the secretion of soluble mediators by end stage osteoarthritis synovial tissue explants reveals a reduced responsiveness to an inflammatory trigger.

Gierman LM, van El B, van der Ham F, Koudijs A, Stoop R, Verheijen JH, Kloppenburg M, van Osch GJ, Stojanovic-Susulic V, Huizinga TW, Zuurmond AM - PLoS ONE (2013)

Soluble mediator secretion by non-stimulated and stimulated synovial tissue explants (STEs) from normal and OA donors.Graphs demonstrate the absolute levels of all soluble mediators, which were significantly (p<0.01) different between A. non-stimulated (black bars) and IL-1α-stimulated (white bars) normal STEs and B. non-stimulated (grey bars) and IL-1α-stimulated (white bars) OA STEs. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643929&req=5

pone-0062634-g002: Soluble mediator secretion by non-stimulated and stimulated synovial tissue explants (STEs) from normal and OA donors.Graphs demonstrate the absolute levels of all soluble mediators, which were significantly (p<0.01) different between A. non-stimulated (black bars) and IL-1α-stimulated (white bars) normal STEs and B. non-stimulated (grey bars) and IL-1α-stimulated (white bars) OA STEs. Data were obtained from pooled supernatants representing the average of 6 STEs per donor and the production in a time period of 7 days. Data are plotted on a log scale. Bars indicate mean concentration (pg/ml culture medium) ± SD.
Mentions: To assess the response to an inflammatory trigger of STEs from normal and OA donors, soluble mediator excretion levels were analyzed in both the non-stimulated and the IL-1α-stimulated condition. For normal STEs, 16 mediators increased significantly (p<0.01) after stimulation with IL-1α (Figure 2A). Unexpectedly, the STEs obtained from OA donors secreted only 3 mediators at a significantly different level after IL-1α stimulation (Figure 2B). An overview of all measured mediators in these supernatants can be consulted in table S1.

Bottom Line: No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients.The effects could be the result of prolonged exposure to an inflammatory environment in OA development.

View Article: PubMed Central - PubMed

Affiliation: TNO, Leiden, The Netherlands.

ABSTRACT

Objective: Evidence is accumulating that synovial tissue plays an active role in osteoarthritis (OA), however, exact understanding of its contribution is lacking. In order to further elucidate its role in the OA process, we aimed to identify the secretion pattern of soluble mediators by synovial tissue and to assess its ability to initiate cartilage degeneration.

Methods: Synovial tissue explants (STEs) obtained from donors without history of OA (n = 8) or from end stage OA patients (n = 16) were cultured alone or together with bovine cartilage explants in the absence or presence of IL-1α. The secretion of 48 soluble mediators was measured and the effect on glycosaminoglycan (GAG) release and matrix metalloproteinase (MMP) activity was determined.

Results: Normal and OA STEs secreted comparable levels of almost all measured soluble mediators. However, in the presence of IL-1α these mediators were less secreted by OA than by normal STEs of which 15 differed significantly (p<0.01). No effect of normal or OA STEs on GAG release from the cartilage explants was observed, and no differences in MMP activity between OA and normal STEs were detected.

Conclusions: Unexpectedly, a comparable secretion profile of soluble mediators was found for OA and normal STEs while the reduced responsiveness of OA STEs to an inflammatory trigger indicates a different state of this tissue in OA patients. The effects could be the result of prolonged exposure to an inflammatory environment in OA development. Further understanding of the pro-inflammatory and inflammation resolving mechanisms during disease progression in synovial tissue may provide valuable targets for therapy in the future.

Show MeSH
Related in: MedlinePlus