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- 저자 : Mao Guping (검색결과 2 건)
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Xu Yiyang,Mao Guping,Long Dianbo,Deng Zengfa,Xin Ruobin,Zhang Ziji,Xue Ting,Liao Weiming,Xu Jie,Kang Yan 생화학분자생물학회 2022 Experimental and molecular medicine Vol.54 No.-
Osteoarthritis, characterized by articular cartilage degradation, is the leading cause of chronic disability in older adults. Studies have indicated that circular RNAs are crucial regulators of chondrocyte development and are involved in the progression of osteoarthritis. In this study, we investigated the function and mechanism of a circular RNA and its potential for osteoarthritis therapy. The expression levels of circCREBBP, screened by circular RNA sequencing during chondrogenic differentiation in adipose tissue-derived stem cells, and TGFβ2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1β-induced chondrocytes. circCREBBP knockdown increased anabolism in the extracellular matrix and inhibited chondrocyte degeneration, whereas circCREBBP overexpression led to the opposite effects. Luciferase reporter assays, rescue experiments, RNA immunoprecipitation, and RNA pulldown assays confirmed that circCREBBP upregulated TGFβ2 expression by sponging miR-1208, resulting in significantly enhanced phosphorylation of Smad1/5 in chondrocytes. Moreover, intra-articular injection of adeno-associated virus-sh-circCrebbp alleviated osteoarthritis in a mouse model of destabilization of the medial meniscus. Our findings reveal a critical role for circCREBBP in the progression of osteoarthritis and provide a potential target for osteoarthritis therapy.
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Shu Hu,Xiaoyi Zhao,Guping Mao,Ziji Zhang,Xingzhao Wen,Chengyun Zhang,Weiming Liao,Zhiqi Zhang 생화학분자생물학회 2019 Experimental and molecular medicine Vol.51 No.-
MicroRNAs (miRNAs, miR) play a key role in the pathogenesis of osteoarthritis (OA). Few studies have examined theregulatory role of P21-activated kinases (PAKs), a family of serine/threonine kinases, in OA. The aim of this study was todetermine whether miR-455-3p can regulate cartilage degeneration in OA by targeting PAK2. MiR-455-3p knockoutmice showed significant degeneration of the knee cartilage. MiR-455-3p expression increased and PAK2 expressiondecreased in the late stage of human adipose-derived stem cell (hADSC) chondrogenesis and in chondrocytesaffected by OA. Furthermore, in both miR-455-3p-overexpressing chondrocytes and PAK2-suppressing chondrocytes,cartilage-specific genes were upregulated, and hypertrophy-related genes were downregulated. A luciferase reporterassay confirmed that miR-455-3p regulates PAK2 expression by directly targeting the 3′-untranslated regions (3′UTRs)of PAK2 mRNA. IPA-3, a PAK inhibitor, inhibited cartilage degeneration due to OA. Moreover, suppressing PAK2promoted R-Smad activation in the TGF/Smad signaling pathway in chondrocytes. Altogether, our results suggest thatmiR-455-3p promotes TGF-β/Smad signaling in chondrocytes and inhibits cartilage degeneration by directlysuppressing PAK2. These results thus indicate that miR-455-3p and PAK2 are novel potential therapeutic agents andtargets, respectively, for the treatment of OA.
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