KMID : 0620920220540101727
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Experimental & Molecular Medicine 2022 Volume.54 No. 10 p.1727 ~ p.1740
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Circular RNA CREBBP modulates cartilage degradation by activating the Smad1/5 pathway through the TGF¥â2/ALK1 axis
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Xu Yiyang
Mao Guping Long Dianbo Deng Zengfa Xin Ruobin Zhang Ziji Xue Ting Liao Weiming Xu Jie Kang Yan
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Abstract
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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 TGF¥â2 were significantly increased in the cartilage of patients with osteoarthritis and IL-1¥â-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 TGF¥â2 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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KEYWORD
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Long non-coding RNAs, Phosphorylation
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