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Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus

Effects of IL-29 on cartilage degradation by OA FLS ex vivo. (a) The OA cartilage depletion after being cocultured with OA FLS for 72 h was visualized in Safranin O/Fast Green-stained sections. Representative images from one experiment are reported (a), and the reduced intensity of red stain denotes proteoglycan loss (original magnification ×100). (b) The depth of GAG depletion (μm) in cartilage was measured from the articular surface to the red/orange tidemark (marked by arrow). (c) The ratio of MM-1, MM-2, MM-3, and MM-13 to TIMP-1 was determined by real-time PCR in OA FLS. (d) MMP-3 in culture supernatants harvested from each well after 72 h was measured by ELISA. The error bars represent mean ± SEM for triplicate experiments. ∗P < 0.05 versus medium control. ∗∗P < 0.01 versus medium control.
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fig5: Effects of IL-29 on cartilage degradation by OA FLS ex vivo. (a) The OA cartilage depletion after being cocultured with OA FLS for 72 h was visualized in Safranin O/Fast Green-stained sections. Representative images from one experiment are reported (a), and the reduced intensity of red stain denotes proteoglycan loss (original magnification ×100). (b) The depth of GAG depletion (μm) in cartilage was measured from the articular surface to the red/orange tidemark (marked by arrow). (c) The ratio of MM-1, MM-2, MM-3, and MM-13 to TIMP-1 was determined by real-time PCR in OA FLS. (d) MMP-3 in culture supernatants harvested from each well after 72 h was measured by ELISA. The error bars represent mean ± SEM for triplicate experiments. ∗P < 0.05 versus medium control. ∗∗P < 0.01 versus medium control.

Mentions: IL-29 can stimulate proinflammatory cytokines expression in OA FLS as shown in Figure 4, and chronic inflammation is a major driver of ongoing cartilage damage and joint degeneration in OA pathogenesis. Therefore, we chose a coculture model of OA FLS with ex vivo cartilage explant to examine the influence of IL-29 on cartilage degradation. After 72 h culture, Safranin O/Fast Green staining of the cartilage in the coculture showed that glycosaminoglycan (GAG) depletion (mean ± SEM) was significantly greater in IL-29 (100 ng/mL) (477.4 ± 22.0 μm) or IL-1β (20 ng/mL) (717.4 ± 20.9 μm) treated conditions than that in the medium alone (154.4 ± 7.1 μm), indicated by the less intense red staining for Safranin O and GAG depletion deeper (Figures 5(a) and 5(b)).


Interleukin-29 Enhances Synovial Inflammation and Cartilage Degradation in Osteoarthritis.

Xu L, Peng Q, Xuan W, Feng X, Kong X, Zhang M, Tan W, Xue M, Wang F - Mediators Inflamm. (2016)

Effects of IL-29 on cartilage degradation by OA FLS ex vivo. (a) The OA cartilage depletion after being cocultured with OA FLS for 72 h was visualized in Safranin O/Fast Green-stained sections. Representative images from one experiment are reported (a), and the reduced intensity of red stain denotes proteoglycan loss (original magnification ×100). (b) The depth of GAG depletion (μm) in cartilage was measured from the articular surface to the red/orange tidemark (marked by arrow). (c) The ratio of MM-1, MM-2, MM-3, and MM-13 to TIMP-1 was determined by real-time PCR in OA FLS. (d) MMP-3 in culture supernatants harvested from each well after 72 h was measured by ELISA. The error bars represent mean ± SEM for triplicate experiments. ∗P < 0.05 versus medium control. ∗∗P < 0.01 versus medium control.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4940582&req=5

fig5: Effects of IL-29 on cartilage degradation by OA FLS ex vivo. (a) The OA cartilage depletion after being cocultured with OA FLS for 72 h was visualized in Safranin O/Fast Green-stained sections. Representative images from one experiment are reported (a), and the reduced intensity of red stain denotes proteoglycan loss (original magnification ×100). (b) The depth of GAG depletion (μm) in cartilage was measured from the articular surface to the red/orange tidemark (marked by arrow). (c) The ratio of MM-1, MM-2, MM-3, and MM-13 to TIMP-1 was determined by real-time PCR in OA FLS. (d) MMP-3 in culture supernatants harvested from each well after 72 h was measured by ELISA. The error bars represent mean ± SEM for triplicate experiments. ∗P < 0.05 versus medium control. ∗∗P < 0.01 versus medium control.
Mentions: IL-29 can stimulate proinflammatory cytokines expression in OA FLS as shown in Figure 4, and chronic inflammation is a major driver of ongoing cartilage damage and joint degeneration in OA pathogenesis. Therefore, we chose a coculture model of OA FLS with ex vivo cartilage explant to examine the influence of IL-29 on cartilage degradation. After 72 h culture, Safranin O/Fast Green staining of the cartilage in the coculture showed that glycosaminoglycan (GAG) depletion (mean ± SEM) was significantly greater in IL-29 (100 ng/mL) (477.4 ± 22.0 μm) or IL-1β (20 ng/mL) (717.4 ± 20.9 μm) treated conditions than that in the medium alone (154.4 ± 7.1 μm), indicated by the less intense red staining for Safranin O and GAG depletion deeper (Figures 5(a) and 5(b)).

Bottom Line: The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA.Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium.Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot.

View Article: PubMed Central - PubMed

Affiliation: Department of Rheumatology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.

ABSTRACT
We have recently shown that IL-29 was an important proinflammatory cytokine in pathogenesis of rheumatoid arthritis (RA). Inflammation also contributes to the pathogenesis of osteoarthritis (OA). The aim of this study was to investigate the effect and mechanism of IL-29 on cytokine production and cartilage degradation in OA. The mRNA levels of IL-29 and its specific receptor IL-28Ra in peripheral blood mononuclear cells (PBMCs) were significantly increased in OA patients when compared to healthy controls (HC). In the serum, IL-29 protein levels were higher in OA patients than those in HC. Immunohistochemistry revealed that both IL-29 and IL-28Ra were dramatically elevated in OA synovium compared to HC; synovial fibroblasts (FLS) and macrophages were the main IL-29-producing cells in OA synovium. Furthermore, recombinant IL-29 augmented the mRNA expression of IL-1β, IL-6, IL-8, and matrix-metalloproteinase-3 (MMP-3) in OA FLS and increased cartilage degradation when ex vivo OA cartilage explant was coincubated with OA FLS. Finally, in OA FLS, IL-29 dominantly activated MAPK and nuclear factor-κB (NF-κB), but not Jak-STAT and AKT signaling pathway as examined by western blot. In conclusion, IL-29 stimulates inflammation and cartilage degradation by OA FLS, indicating that this cytokine is likely involved in the pathogenesis of OA.

No MeSH data available.


Related in: MedlinePlus