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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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연구자들이 자신의 연구와 전문성을 널리 알리고, 새로운 협력의 기회를 만들 수 있는 네트워킹 공간이에요.
논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2019.1
- 수록면
- 336 - 341 (6page)
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The cGAS-STING pathway plays an important role in pathogen-induced activation of the innate immune response. The 29-kDa amino-terminal fibronectin fragment (29-kDa FN-f) found predominantly in the synovial fluid of osteoarthritis (OA) patients increases the expression of catabolic factors via the toll-like receptor-2 (TLR-2) signaling pathway. In this study, we investigated whether 29-kDa FN-f induces inflammatory responses via the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway in human primary chondrocytes. The levels of cGAS and STING were elevated in OA cartilage compared with normal cartilage. Long-term treatment of chondrocytes with 29-kDa FN-f activated the cGAS/STING pathway together with the increased level of gamma-H2AX, a marker of DNA breaks. In addition, the expression of pro-inflammatory cytokines, including granulocytemacrophage colony-stimulating factor (GM-CSF/CSF-2), granulocyte colony-stimulating factor (G-CSF/CSF-3), and type I interferon (IFN-), was increased more than 100-fold in 29-kDa FN-f-treated chondrocytes. However, knockdown of cGAS and STING suppressed 29-kDa FN-f-induced expression of GM-CSF, G-CSF, and IFN- together with the decreased activation of TANK-binding kinase 1 (TBK1), interferon regulatory factor 3 (IRF3), and inhibitor protein B (IB). Furthermore, NOD2 or TLR-2 knockdown suppressed the expression of GM-CSF, G-CSF, and IFN- as well as decreased the activation of the cGAS/STING pathway in 29-kDa FN-f-treated chondrocytes. These data demonstrate that the cGAS/STING/TBK1/IRF3 pathway plays a critical role in 29-kDa FN-f-induced expression of pro-inflammatory cytokines.
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참고문헌 (45)
참고문헌 신청
Goldring MB / 2000 / The role of the chondrocyte in osteoarthritis / Arthritis Rheum 43:1916~1926
Goldring MB / 2007 / Osteoarthritis / J Cell Physiol 213:626~634
Goldring SR / 2004 / The role of cytokines in cartilage matrix degeneration in osteoarthritis / Clin Orthop Relat Res :S27~S36
Rosenberg JH / 2017 / Damage-associated molecular patterns in the pathogenesis of osteoarthritis : potentially novel therapeutic targets / Mol Cell Biochem 434:171~179
Rosenberg JH / 2017 / Increased expression of damageassociated molecular patterns(DAMPs)in osteoarthritis of human knee joint compared to hip joint / Mol Cell Biochem 436:59~69
Goldring MB / 2007 / Osteoarthritis / J Cell Physiol 213:626~634
Goldring SR / 2004 / The role of cytokines in cartilage matrix degeneration in osteoarthritis / Clin Orthop Relat Res :S27~S36
Rosenberg JH / 2017 / Damage-associated molecular patterns in the pathogenesis of osteoarthritis : potentially novel therapeutic targets / Mol Cell Biochem 434:171~179
Rosenberg JH / 2017 / Increased expression of damageassociated molecular patterns(DAMPs)in osteoarthritis of human knee joint compared to hip joint / Mol Cell Biochem 436:59~69
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