Crosstalk between FLS and chondrocytes is regulated by HIF-2alpha-mediated cytokines in arthritis
Experimental & Molecular Medicine
;
: e197-2015.
Article
in English
| WPRIM
| ID: wpr-228160
ABSTRACT
Rheumatoid arthritis (RA) and osteoarthritis (OA), two common types of arthritis, affect the joints mainly by targeting the synovium and cartilage. Increasing evidence indicates that a significant network connects synovitis and cartilage destruction during the progression of arthritis. We recently demonstrated that hypoxia-inducible factor (HIF)-2alpha causes RA and OA by regulating the expression of catabolic factors in fibroblast-like synoviocytes (FLS) or chondrocytes. To address the reciprocal influences of HIF-2alpha on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2alpha-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-alpha treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2alpha-overexpressing FLS exhibited upregulation of Mmp3 and Mmp13, which is similar to the effects induced by interleukin (IL)-6 treatment of chondrocytes. We confirmed these differential HIF-2alpha-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-alpha-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-alpha neutralization blocked the alterations in gene expression associated with co-culture of FLS with chondrocytes. Our results further suggested that the observed changes might reflect the HIF-2alpha-induced upregulation of specific receptors for TNF-alpha (in FLS) and IL-6 (in chondrocytes). This study broadens our understanding of the possible regulatory mechanisms underlying the crosstalk between the synovium and cartilage in the presence of HIF-2alpha, and may suggest potential new anti-arthritis therapies.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteoarthritis
/
Arthritis
/
Arthritis, Rheumatoid
/
Synovial Membrane
/
Up-Regulation
/
Cells, Cultured
/
Gene Expression Regulation
/
Interleukin-6
/
Tumor Necrosis Factor-alpha
/
Coculture Techniques
Limits:
Animals
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2015
Type:
Article
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