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- 학술저널
- 저자정보
- 발행연도
- 2015.1
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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)-2α 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-2α on FLS and chondrocytes, we applied an in vitro co-culture system using a transwell apparatus. When co-cultured with HIF-2α-overexpressing chondrocytes, FLS exhibited increased expression of matrix metalloproteinases and inflammatory mediators, similar to the effects induced by tumor-necrosis factor (TNF)-α treatment of FLS. Moreover, chondrocytes co-cultured with HIF-2α-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-2α-induced effects via distinct secretory mediators using Il6-knockout cells and a TNF-α-blocking antibody. The FLS-co-culture-induced gene expression changes in chondrocytes were significantly abrogated by IL-6 deficiency, whereas TNF-α 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-2α-induced upregulation of specific receptors for TNF-α (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-2α, and may suggest potential new anti-arthritis therapies.
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참고문헌 (26)
참고문헌 신청
Alaaeddine N / 2015 / The chemokine CCL20 induces proinflammatory and matrix degradative responses in cartilage / Inf
Bartok B / 2010 / Fibroblast-like synoviocytes : key effector cells in rheumatoid arthritis / Immunol Rev 233 : 233 ~ 255
Bottini N / 2013 / Duality of fibroblast-like synoviocytes in RA : passive responders and imprinted aggressors / Nat Rev Rheumatol 9 : 24 ~ 33
Firestein GS / 2003 / Evolving concepts of rheumatoid arthritis / Nature 423 : 356 ~ 361
Gaber T / 2005 / Hypoxia inducible factor(HIF)in rheumatology : low O2! See what HIF can do! / Ann Rheum Dis 64 : 971 ~ 980
Bartok B / 2010 / Fibroblast-like synoviocytes : key effector cells in rheumatoid arthritis / Immunol Rev 233 : 233 ~ 255
Bottini N / 2013 / Duality of fibroblast-like synoviocytes in RA : passive responders and imprinted aggressors / Nat Rev Rheumatol 9 : 24 ~ 33
Firestein GS / 2003 / Evolving concepts of rheumatoid arthritis / Nature 423 : 356 ~ 361
Gaber T / 2005 / Hypoxia inducible factor(HIF)in rheumatology : low O2! See what HIF can do! / Ann Rheum Dis 64 : 971 ~ 980
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