Increased IL-6 receptor expression and signaling in ageing cartilage can be explained by loss of TGF-β-mediated IL-6 receptor suppression
In: Osteoarthritis and cartilage, Jg. 29 (2020-04-09), Heft 5
Online
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Summary Objective Osteoarthritis (OA) development is strongly associated with ageing, possibly due to age-related changes in transforming growth factor-β (TGF-β) signaling in cartilage. Recently, we showed that TGF-β suppresses interleukin (IL)-6 receptor (IL-6R) expression in chondrocytes. As IL-6 is involved in cartilage degeneration, we hypothesized that age-related loss of TGF-β signaling results in increased IL-6R expression and signaling in ageing cartilage. Design Bovine articular cartilage was collected and immediately processed to study age-related changes in IL-6R expression using qPCR and IHC (age-range: 0.5–14 years). Moreover, cartilage from young and aged cows was stimulated with rhIL-6 and/or rhTGF-β1 to measure IL-6-induced p-STAT3 using Western blot. Expression of STAT3-responsive genes was analyzed using qPCR. Results Expression of IL-6 receptor (bIL-6R) significantly increased in cartilage upon ageing (slope: 0.32, 95%CI: 0.20–0.45), while expression of glycoprotein 130 (bGP130) was unaffected. Cartilage stimulation with IL-6 showed increased induction of p-STAT3 upon ageing (slope: 0.14, 95%CI: 0.08–0.20). Furthermore, IL-6-mediated induction of STAT3-responsive genes like bSOCS3 and bMMP3 was increased in aged compared to young cartilage. Interestingly, the ability of TGF-β to suppress bIL6R expression in young cartilage was lost upon ageing (slope: 0.21, 95%CI: 0.13–0.30). Concurrently, an age-related loss in TGF-β-mediated suppression of IL-6-induced p-STAT3 and bSOCS3 expression was observed. Conclusions Ageing results in enhanced IL-6R expression and subsequent IL-6-induced p-STAT3 signaling in articular cartilage. This is likely caused by age-related loss of protective TGF-β signaling, resulting in loss of TGF-β-mediated IL-6R suppression. Because of the detrimental role of IL-6 in cartilage, this mechanism may be involved in age-related OA development.
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Increased IL-6 receptor expression and signaling in ageing cartilage can be explained by loss of TGF-β-mediated IL-6 receptor suppression
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Autor/in / Beteiligte Person: | Koenders, Marije I. ; A. van Caam ; H.M. van Beuningen ; M. van Laar ; Wiegertjes, R. ; Thielen, N. ; P.L.E.M. van Lent ; E.N. Blaney Davidson ; F.A.J. van de Loo ; P.M. van der Kraan |
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Zeitschrift: | Osteoarthritis and cartilage, Jg. 29 (2020-04-09), Heft 5 |
Veröffentlichung: | 2020 |
Medientyp: | unknown |
ISSN: | 1522-9653 (print) |
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