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

M Chabaud; E Lubberts; L Joosten; W van Den Berg; P Miossec

doi:10.1186/ar294

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

Arthritis Res. 2001;3(3):168-77. doi: 10.1186/ar294. Epub 2001 Jan 26.

Authors

M Chabaud¹, E Lubberts, L Joosten, W van Den Berg, P Miossec

Affiliation

¹ INSERM U403, Faculté de Médecine Laennec, and Departments of Immunology and Rheumatology, Hôpital Edouard Herriot, Lyon, France.

PMID: 11299057
PMCID: PMC30709
DOI: 10.1186/ar294

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Blocking / pharmacology
Antibodies, Monoclonal / pharmacology
Arthritis, Rheumatoid / metabolism*
Bone and Bones / drug effects*
Bone and Bones / metabolism
Cartilage, Articular / drug effects
Cartilage, Articular / metabolism
Cartilage, Articular / pathology
Chondrocytes / drug effects
Chondrocytes / metabolism
Collagen / metabolism
Drug Combinations
Injections, Intra-Articular
Insulin-Like Growth Factor I / pharmacology
Interleukin-1 / pharmacology
Interleukin-17 / administration & dosage
Interleukin-17 / immunology
Interleukin-17 / pharmacology*
Interleukin-6 / biosynthesis
Knee Joint / drug effects
Knee Joint / metabolism
Knee Joint / pathology
Mice
Mice, Inbred C57BL
Proteoglycans / biosynthesis
Synovial Membrane / drug effects*
Synovial Membrane / metabolism

Substances

Antibodies, Blocking
Antibodies, Monoclonal
Drug Combinations
Interleukin-1
Interleukin-17
Interleukin-6
Proteoglycans
Insulin-Like Growth Factor I
Collagen