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论文题目: miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2
英文论文题目: miR-146a facilitates osteoarthritis by regulating cartilage homeostasis via targeting Camk2d and Ppp3r2
第一作者: Zhang, XD; Wang, CD; Zhao, JY; Xu, JJ; Geng, YY; Dai, LM; Huang, Y; Fu, SC; Dai, KR; Zhang, XL
英文第一作者: Zhang, XD; Wang, CD; Zhao, JY; Xu, JJ; Geng, YY; Dai, LM; Huang, Y; Fu, SC; Dai, KR; Zhang, XL
联系作者: Dai, KR; Zhang, XL (reprint author), Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
英文联系作者: Dai, KR; Zhang, XL (reprint author), Chinese Acad Sci, Key Lab Stem Cell Biol, Inst Hlth Sci, Shanghai Inst Biol Sci, 320 Yueyang Rd, Shanghai 200031, Peoples R China.
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发表年度: 2017
卷: 8
期:
页码: e2734
摘要: Osteoarthritis (OA), characterized by insufficient extracellular matrix synthesis and cartilage degeneration, is known as an incurable disease because its pathogenesis is poorly elucidated. Thus far, limited information is available regarding the pathophysiological role of microRNAs (miRNAs) in OA. In this study, we investigated the specific function of miR-146a in OA pathophysiology using mouse OA models. We found that the articular cartilage degeneration of miR-146a knockout (KO) mice was alleviated compared with that of the wild-type (WT) mice in spontaneous and instability-induced OA models. We demonstrate that miR-146a aggravated pro-inflammatory cytokines induced suppressing the expression of cartilage matrix-associated genes. We further identified calcium/calmodulin-dependent protein kinase II delta (Camk2d) and protein phosphatase 3, regulatory subunit B, beta isoform (Ppp3r2, also known as calcineurin B, type II) were essential targets of miR-146a in regulating cartilage homeostasis. Moreover, we found that surgical-induced OA mice treated with a miR-146a inhibitor significantly alleviated the destruction of articular cartilage via targeting Camk2d and Ppp3r2. These results suggested that miR-146a has a crucial role in maintaining cartilage homeostasis. MiR-146a inhibition in chondrocytes can be a potential therapeutic strategy to ameliorate OA.
英文摘要: Osteoarthritis (OA), characterized by insufficient extracellular matrix synthesis and cartilage degeneration, is known as an incurable disease because its pathogenesis is poorly elucidated. Thus far, limited information is available regarding the pathophysiological role of microRNAs (miRNAs) in OA. In this study, we investigated the specific function of miR-146a in OA pathophysiology using mouse OA models. We found that the articular cartilage degeneration of miR-146a knockout (KO) mice was alleviated compared with that of the wild-type (WT) mice in spontaneous and instability-induced OA models. We demonstrate that miR-146a aggravated pro-inflammatory cytokines induced suppressing the expression of cartilage matrix-associated genes. We further identified calcium/calmodulin-dependent protein kinase II delta (Camk2d) and protein phosphatase 3, regulatory subunit B, beta isoform (Ppp3r2, also known as calcineurin B, type II) were essential targets of miR-146a in regulating cartilage homeostasis. Moreover, we found that surgical-induced OA mice treated with a miR-146a inhibitor significantly alleviated the destruction of articular cartilage via targeting Camk2d and Ppp3r2. These results suggested that miR-146a has a crucial role in maintaining cartilage homeostasis. MiR-146a inhibition in chondrocytes can be a potential therapeutic strategy to ameliorate OA.
刊物名称: CELL DEATH & DISEASE
英文刊物名称: CELL DEATH & DISEASE
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学科: Cell Biology
英文学科: Cell Biology
影响因子: 5.965
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论文类别: Article
英文论文类别: Article
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