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Synovitis associated with osteoarthritis (OA) is directly responsible for several clinical symptoms and reflects OA's structural progression. This study sought to analyze the expression of proinflammatory mediations, including Interleukin (IL)-17 and IL-22, which play key roles in regulating inflammatory processes, in inflamed and non-inflamed areas of osteoarthritic synovium.Synovium from knees of 32 OA patients were collected at surgery. Macroscopic evaluation of inflammation enabled inflamed and non-inflamed areas to be separated. Samples were incubated to obtain tissue-conditioned media. Quantitative mRNA expression of proinflammatory mediators was analyzed by RT-PCR and protein levels by ELISA and gelatin zymography. Immunohistochemistry and histology were performed.Inflamed synovium were characterized by increased leukocyte infiltration and a higher vessel-to-tissue area ratio than non-inflamed tissues. Macrophages, T and B lymphocytes, and some neutrophils were found only in the inflamed tissue, and only in the subintimal layer. Levels of proinflammatory cytokines and MMP-9 were significantly higher in tissue-conditioned media from inflamed than non-inflamed tissues. Inflamed areas were associated with higher expression of IL-17 and IL-22, both correlated with the combined release of IL-6, IL-23, and TGFβ1.Our results showed that inflammatory cytokines, including IL-17 and IL-22, are expressed at higher levels by inflamed OA synovium and suggest IL-22 involvement in OA pathophysiology. This study will help identify new therapeutic strategies for OA, especially the targeting of IL-22 to decrease inflammation.

Original publication

DOI

10.1016/j.joca.2014.12.007

Type

Journal article

Journal

Osteoarthritis and cartilage

Publication Date

11/2015

Volume

23

Pages

1843 - 1852

Addresses

Sorbonne University, UPMC Univ Paris 06, UMR_S 938, F-75005 Paris, France; INSERM UMR_S938, UPMC Univ Paris 06, F-75012 Paris, France; Inflammation-Immunopathology-Biotherapy Department (DHU i2B), 184 rue du Faubourg Saint-Antoine, F-75012 Paris, France.

Keywords

Synovial Membrane, Humans, Osteoarthritis, Knee, Synovitis, RNA, Interleukins, Interleukin-17, Enzyme-Linked Immunosorbent Assay, Immunohistochemistry, Gene Expression Regulation, Aged, Aged, 80 and over, Middle Aged, Female, Male, Real-Time Polymerase Chain Reaction