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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

Secreted MMP activity of STEs and cartilage explants cultured alone or together.After 7 days, the MMP-activity (rfu/sec) was determined (in culture medium) of normal (A, B) and OA (C, D) STEs and healthy cartilage explants, cultured alone or together, without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and demonstrates the activity of STEs alone (left), STEs together with cartilage explants (middle) or cartilage explants cultured alone (right). The MMP activity in the medium of STEs cultured alone was higher, compared to the MMP activity in the co-culture conditions. Significance levels are indicated.
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pone-0062634-g004: Secreted MMP activity of STEs and cartilage explants cultured alone or together.After 7 days, the MMP-activity (rfu/sec) was determined (in culture medium) of normal (A, B) and OA (C, D) STEs and healthy cartilage explants, cultured alone or together, without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and demonstrates the activity of STEs alone (left), STEs together with cartilage explants (middle) or cartilage explants cultured alone (right). The MMP activity in the medium of STEs cultured alone was higher, compared to the MMP activity in the co-culture conditions. Significance levels are indicated.

Mentions: To assess for collagen degrading enzymes, MMP activity was measured in the different culture conditions. Remarkably, the MMP activity in the medium of non-stimulated normal and OA STEs cultured alone was significantly higher than in the co-cultures (p<0.01, Figure 4A,C). This was also observed for the IL-1α-stimulated OA condition (Figure 4D; p<0.05). A trend was observed in the IL-1α-stimulated normal condition (Figure 4B; p<0.1). IL-1α stimulation did not led to significantly more MMP activity when normal or OA STE was cultured alone (table 2). IL-1α stimulation yielded significantly more MMP activity in the co-cultures with OA STE while this was not the case for normal STE culture conditions. This is probably due to the fact that bovine cartilage donors used in the OA STE conditions were more prone to IL-1α stimulation with respect to MMP activity than those used in normal STE conditions (table 2).


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)

Secreted MMP activity of STEs and cartilage explants cultured alone or together.After 7 days, the MMP-activity (rfu/sec) was determined (in culture medium) of normal (A, B) and OA (C, D) STEs and healthy cartilage explants, cultured alone or together, without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and demonstrates the activity of STEs alone (left), STEs together with cartilage explants (middle) or cartilage explants cultured alone (right). The MMP activity in the medium of STEs cultured alone was higher, compared to the MMP activity in the co-culture conditions. Significance levels are indicated.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062634-g004: Secreted MMP activity of STEs and cartilage explants cultured alone or together.After 7 days, the MMP-activity (rfu/sec) was determined (in culture medium) of normal (A, B) and OA (C, D) STEs and healthy cartilage explants, cultured alone or together, without (A, C) or with (B, D) IL-1α stimulation. Each line represents an individual donor and demonstrates the activity of STEs alone (left), STEs together with cartilage explants (middle) or cartilage explants cultured alone (right). The MMP activity in the medium of STEs cultured alone was higher, compared to the MMP activity in the co-culture conditions. Significance levels are indicated.
Mentions: To assess for collagen degrading enzymes, MMP activity was measured in the different culture conditions. Remarkably, the MMP activity in the medium of non-stimulated normal and OA STEs cultured alone was significantly higher than in the co-cultures (p<0.01, Figure 4A,C). This was also observed for the IL-1α-stimulated OA condition (Figure 4D; p<0.05). A trend was observed in the IL-1α-stimulated normal condition (Figure 4B; p<0.1). IL-1α stimulation did not led to significantly more MMP activity when normal or OA STE was cultured alone (table 2). IL-1α stimulation yielded significantly more MMP activity in the co-cultures with OA STE while this was not the case for normal STE culture conditions. This is probably due to the fact that bovine cartilage donors used in the OA STE conditions were more prone to IL-1α stimulation with respect to MMP activity than those used in normal STE conditions (table 2).

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