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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2018.1
- 수록면
- 508 - 513 (6page)
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Fibronectin fragments found in the synovial fluid of patients with osteoarthritis (OA) induce the catabolic responses in cartilage. Nuclear high-mobility group protein Box 1 (HMGB1), a damage-associated molecular pattern, is responsible for the regulation of signaling pathways related to cell death and survival in response to various stimuli. In this study, we investigated whether changes induced by 29-kDa aminoterminal fibronectin fragment (29-kDa FN-f) in HMGB1 expression influences the pathogenesis of OA via an HMGB1- modulated autophagy signaling pathway. Human articular chondrocytes were enzymatically isolated from articular cartilage. The level of mRNA was measured by quantitative real-time PCR. The expression of proteins was examined by western blot analysis, immnunofluorescence assay, and enzyme-linked immunosorbent assay. Interaction of proteins was evaluated by immunoprecipitation. The HMGB1 level was significantly lower in human OA cartilage than in normal cartilage. Although 29-kDa FN-f significantly reduced the HMGB1 expression at the mRNA and protein levels 6 h after treatment, the cytoplasmic level of HMGB1 was increased in chondrocytes treated with 29-kDa FN-f, which significantly inhibited the interaction of HMGB1 with Beclin-1, increased the interaction of Bcl-2 with Beclin-1, and decreased the levels of Beclin-1 and phosphorylated Bcl-2. In addition, the level of microtubule-associated protein 1 light chain 3-II, an autophagy marker, was down-regulated in chondrocytes treated with 29-kDa FN-f, whereas the effect was antagonized by mTOR knockdown. Furthermore, prolonged treatment with 29-kDa FN-f significantly increased the release of HMGB1 into the culture medium. These results demonstrated that 29-kDa FN-f inhibits chondrocyte autophagy by modulating the HMGB1 signaling pathway.
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참고문헌 (4)
참고문헌 신청
Md. Ataur Rahman / 2017 / Therapeutic implication of autophagy in neurodegenerative diseases / BMB Reports 50(7):345~354
이신애 / 2014 / The Role of High Mobility Group Box 1 in Innate Immunity / Yonsei Medical Journal 55(5):1165~1176
황현숙 / 2015 / PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model / BMB Reports 48(7):407~412
Shazie Yusein-Myashkova / 2016 / Non-histone protein HMGB1 inhibits the repair of damaged DNA by cisplatin in NIH-3T3 murine fibroblasts / BMB Reports 49(2):99~104
이신애 / 2014 / The Role of High Mobility Group Box 1 in Innate Immunity / Yonsei Medical Journal 55(5):1165~1176
황현숙 / 2015 / PEP-1-FK506BP12 inhibits matrix metalloproteinase expression in human articular chondrocytes and in a mouse carrageenan-induced arthritis model / BMB Reports 48(7):407~412
Shazie Yusein-Myashkova / 2016 / Non-histone protein HMGB1 inhibits the repair of damaged DNA by cisplatin in NIH-3T3 murine fibroblasts / BMB Reports 49(2):99~104
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