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IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.

Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P - Arthritis Res. (2001)

Bottom Line: In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants.Addition of IL-1 in these conditions increased the effect of IL-17.In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

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Effect of intra-articular administration of IL-17 on cartilage destruction. Naive C57Bl/6 mice were intra-articulately injected into the knee joint with recombinant murine IL-17 (100 ng/ml) at days 0 and 3 (b and d). The contralateral joint received an equal volume (6 μl) of saline (a and c). Knee joints were taken for histology 2 days after the last injection. Proteoglycan depletion was analyzed using Safranin O staining. Cartilage depletion was visualized by diminished staining of the matrix. The effect of IL-17 can be seen as the lighter (b and d) rather than the darker staining (a and c) in cartilage. (a) and (b), Original magnification, × 50; (c) and (d), original magnification × 200. P, Patella; F, femur; JS, joint space; C, cartilage.
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Figure 8: Effect of intra-articular administration of IL-17 on cartilage destruction. Naive C57Bl/6 mice were intra-articulately injected into the knee joint with recombinant murine IL-17 (100 ng/ml) at days 0 and 3 (b and d). The contralateral joint received an equal volume (6 μl) of saline (a and c). Knee joints were taken for histology 2 days after the last injection. Proteoglycan depletion was analyzed using Safranin O staining. Cartilage depletion was visualized by diminished staining of the matrix. The effect of IL-17 can be seen as the lighter (b and d) rather than the darker staining (a and c) in cartilage. (a) and (b), Original magnification, × 50; (c) and (d), original magnification × 200. P, Patella; F, femur; JS, joint space; C, cartilage.

Mentions: To extend these results to an in vivo situation, murine IL-17 was injected into mouse knee joints. We used normal mice to investigate solely the direct contribution of IL-17. Whole knee sections were stained for cartilage proteoglycan content. Figure 8 shows that profound proteoglycan depletion was observed in the IL-17 treated group when compared with the control group. These findings extend the catabolic effects of IL-17 on cartilage degradation to the in vivo situation.


IL-17 derived from juxta-articular bone and synovium contributes to joint degradation in rheumatoid arthritis.

Chabaud M, Lubberts E, Joosten L, van Den Berg W, Miossec P - Arthritis Res. (2001)

Effect of intra-articular administration of IL-17 on cartilage destruction. Naive C57Bl/6 mice were intra-articulately injected into the knee joint with recombinant murine IL-17 (100 ng/ml) at days 0 and 3 (b and d). The contralateral joint received an equal volume (6 μl) of saline (a and c). Knee joints were taken for histology 2 days after the last injection. Proteoglycan depletion was analyzed using Safranin O staining. Cartilage depletion was visualized by diminished staining of the matrix. The effect of IL-17 can be seen as the lighter (b and d) rather than the darker staining (a and c) in cartilage. (a) and (b), Original magnification, × 50; (c) and (d), original magnification × 200. P, Patella; F, femur; JS, joint space; C, cartilage.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC30709&req=5

Figure 8: Effect of intra-articular administration of IL-17 on cartilage destruction. Naive C57Bl/6 mice were intra-articulately injected into the knee joint with recombinant murine IL-17 (100 ng/ml) at days 0 and 3 (b and d). The contralateral joint received an equal volume (6 μl) of saline (a and c). Knee joints were taken for histology 2 days after the last injection. Proteoglycan depletion was analyzed using Safranin O staining. Cartilage depletion was visualized by diminished staining of the matrix. The effect of IL-17 can be seen as the lighter (b and d) rather than the darker staining (a and c) in cartilage. (a) and (b), Original magnification, × 50; (c) and (d), original magnification × 200. P, Patella; F, femur; JS, joint space; C, cartilage.
Mentions: To extend these results to an in vivo situation, murine IL-17 was injected into mouse knee joints. We used normal mice to investigate solely the direct contribution of IL-17. Whole knee sections were stained for cartilage proteoglycan content. Figure 8 shows that profound proteoglycan depletion was observed in the IL-17 treated group when compared with the control group. These findings extend the catabolic effects of IL-17 on cartilage degradation to the in vivo situation.

Bottom Line: In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants.Addition of IL-1 in these conditions increased the effect of IL-17.In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

View Article: PubMed Central - HTML - PubMed

Affiliation: INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

ABSTRACT
The origin and role of IL-17, a T-cell derived cytokine, in cartilage and bone destruction during rheumatoid arthritis (RA) remain to be clarified. In human ex vivo models, addition of IL-17 enhanced IL-6 production and collagen destruction, and inhibited collagen synthesis by RA synovium explants. On mouse cartilage, IL-17 enhanced cartilage proteoglycan loss and inhibited its synthesis. On human RA bone explants, IL-17 also increased bone resorption and decreased formation. Addition of IL-1 in these conditions increased the effect of IL-17. Blocking of bone-derived endogenous IL-17 with specific inhibitors resulted in a protective inhibition of bone destruction. Conversely, intra-articular administration of IL-17 into a normal mouse joint induced cartilage degradation. In conclusion, the contribution of IL-17 derived from synovium and bone marrow T cells to joint destruction suggests the control of IL-17 for the treatment of RA.

Show MeSH
Related in: MedlinePlus