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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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Respective contribution of endogenous IL-17 to synovium and bone destruction. Paired bone and synovium pieces from the same joint in two RA patients were cultured for 7 days in the presence of sIL-17R (1 μg/ml). CTX production in supernatants was measured by ELISA, and results are expressed in nanomoles.
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Figure 7: Respective contribution of endogenous IL-17 to synovium and bone destruction. Paired bone and synovium pieces from the same joint in two RA patients were cultured for 7 days in the presence of sIL-17R (1 μg/ml). CTX production in supernatants was measured by ELISA, and results are expressed in nanomoles.

Mentions: Previous studies regarding the in situ bone environment have demonstrated that juxta-articular bone itself can produce as many cytokines as the inflamed synovium from the same joint [25]. This was first described for cytokines produced by monocytes and mesenchymal cells such as IL-6 and leukemia inhibitory factor. To look at the potential contribution of bone-derived T-cell cytokines, namely IL-17, we performed similar blocking experiments with bone cultures. The sIL-17R was added at the onset of bone culture, and CTX release in supernatants was analyzed by ELISA. Results show that sIL-17R could reduce CTX release by a mean of 64% in bone cultures (Fig. 6b). Paired samples of bone and synovium were available from the same joint for two patients. These samples, as shown in Figure 7, indicated a much higher rate of collagen destruction in bone when compared with synovium. More importantly, sIL-17R induced a very profound reduction of CTX release by bone pieces (134.2 ± 63.7 ng/ml without versus 45.5 ± 8.8 ng/ml with sIL-17R; P < 0.05). Similar results were obtained with synovium pieces (12.6 ± 0.2 ng/ml without sIL-17R versus 4.6 ± 0.8 ng/ml with sIL-17R; P < 0.05). These final results demonstrate the direct contribution of endogenous IL-17 to synovium and, moreover, to bone destruction in RA. They suggest, in particular, that a T-cell subset secreting IL-17 inside bone can contribute significantly to bone destruction.


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)

Respective contribution of endogenous IL-17 to synovium and bone destruction. Paired bone and synovium pieces from the same joint in two RA patients were cultured for 7 days in the presence of sIL-17R (1 μg/ml). CTX production in supernatants was measured by ELISA, and results are expressed in nanomoles.
© Copyright Policy
Related In: Results  -  Collection

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

Figure 7: Respective contribution of endogenous IL-17 to synovium and bone destruction. Paired bone and synovium pieces from the same joint in two RA patients were cultured for 7 days in the presence of sIL-17R (1 μg/ml). CTX production in supernatants was measured by ELISA, and results are expressed in nanomoles.
Mentions: Previous studies regarding the in situ bone environment have demonstrated that juxta-articular bone itself can produce as many cytokines as the inflamed synovium from the same joint [25]. This was first described for cytokines produced by monocytes and mesenchymal cells such as IL-6 and leukemia inhibitory factor. To look at the potential contribution of bone-derived T-cell cytokines, namely IL-17, we performed similar blocking experiments with bone cultures. The sIL-17R was added at the onset of bone culture, and CTX release in supernatants was analyzed by ELISA. Results show that sIL-17R could reduce CTX release by a mean of 64% in bone cultures (Fig. 6b). Paired samples of bone and synovium were available from the same joint for two patients. These samples, as shown in Figure 7, indicated a much higher rate of collagen destruction in bone when compared with synovium. More importantly, sIL-17R induced a very profound reduction of CTX release by bone pieces (134.2 ± 63.7 ng/ml without versus 45.5 ± 8.8 ng/ml with sIL-17R; P < 0.05). Similar results were obtained with synovium pieces (12.6 ± 0.2 ng/ml without sIL-17R versus 4.6 ± 0.8 ng/ml with sIL-17R; P < 0.05). These final results demonstrate the direct contribution of endogenous IL-17 to synovium and, moreover, to bone destruction in RA. They suggest, in particular, that a T-cell subset secreting IL-17 inside bone can contribute significantly to bone destruction.

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