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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

Proteoglycan degradation of healthy cartilage explants cultured alone or together with synovial tissue explants (STEs).Proteoglycan degradation was expressed as the percentage of glycosaminoglycans (GAG) released into the medium during 7 days of culture of cartilage alone or co-cultured together with normal (A, B) or OA (C, D) STEs without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and connects the % GAG release of cartilage alone (left) with the matching co-culture condition of cartilage together with STEs (right). There were no significant differences between cartilage cultured alone or co-cultured with normal or OA STEs.
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pone-0062634-g003: Proteoglycan degradation of healthy cartilage explants cultured alone or together with synovial tissue explants (STEs).Proteoglycan degradation was expressed as the percentage of glycosaminoglycans (GAG) released into the medium during 7 days of culture of cartilage alone or co-cultured together with normal (A, B) or OA (C, D) STEs without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and connects the % GAG release of cartilage alone (left) with the matching co-culture condition of cartilage together with STEs (right). There were no significant differences between cartilage cultured alone or co-cultured with normal or OA STEs.

Mentions: Based on multiplex analysis we questioned if there was also a different effect of normal and OA STEs on cartilage degradation. Hereto, we used an in vitro co-culture model in which cartilage explants were cultured together with STEs. Co-culturing with normal or OA STEs did not induce additional GAG release above the basal release of cartilage explants in non- and IL-1α-stimulated culture conditions (Figure 3). IL-1α stimulation led to significantly more GAG release in all culture conditions (table 1). When comparing absolute values, normal and OA donors differed significantly, however, this was due to a significant difference in basal release of the cartilage explants and not for additional GAG release induced by STEs (indicated in table 1 by the calculated delta (Δ)).


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)

Proteoglycan degradation of healthy cartilage explants cultured alone or together with synovial tissue explants (STEs).Proteoglycan degradation was expressed as the percentage of glycosaminoglycans (GAG) released into the medium during 7 days of culture of cartilage alone or co-cultured together with normal (A, B) or OA (C, D) STEs without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and connects the % GAG release of cartilage alone (left) with the matching co-culture condition of cartilage together with STEs (right). There were no significant differences between cartilage cultured alone or co-cultured with normal or OA STEs.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062634-g003: Proteoglycan degradation of healthy cartilage explants cultured alone or together with synovial tissue explants (STEs).Proteoglycan degradation was expressed as the percentage of glycosaminoglycans (GAG) released into the medium during 7 days of culture of cartilage alone or co-cultured together with normal (A, B) or OA (C, D) STEs without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and connects the % GAG release of cartilage alone (left) with the matching co-culture condition of cartilage together with STEs (right). There were no significant differences between cartilage cultured alone or co-cultured with normal or OA STEs.
Mentions: Based on multiplex analysis we questioned if there was also a different effect of normal and OA STEs on cartilage degradation. Hereto, we used an in vitro co-culture model in which cartilage explants were cultured together with STEs. Co-culturing with normal or OA STEs did not induce additional GAG release above the basal release of cartilage explants in non- and IL-1α-stimulated culture conditions (Figure 3). IL-1α stimulation led to significantly more GAG release in all culture conditions (table 1). When comparing absolute values, normal and OA donors differed significantly, however, this was due to a significant difference in basal release of the cartilage explants and not for additional GAG release induced by STEs (indicated in table 1 by the calculated delta (Δ)).

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