Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis.
Exosome-transported circRNA_0001236 enhances chondrogenesis and suppress cartilage degradation via the miR-3677-3p/Sox9 axis.
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DOI：
10.1186/s13287-021-02431-5
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发表时间：
2021-07-13
影响因子：
7.5
通讯作者：
Kang Y
中科院分区：
文献类型：
--
作者：
Mao G;Xu Y;Long D;Sun H;Li H;Xin R;Zhang Z;Li Z;Yang Z;Kang Y
Aberrations in exosomal circular RNA (circRNA) expression have been identified in various human diseases. In this study, we investigated whether exosomal circRNAs could act as competing endogenous RNAs (ceRNAs) to regulate the pathological process of osteoarthritis (OA). This study aimed to elucidate the specific MSC-derived exosomal circRNAs responsible for MSC-mediated chondrogenic differentiation using human bone marrow-derived MSCs (hMSCs) and a destabilization of the medial meniscus (DMM) mouse model of OA. Exosomal circRNA deep sequencing was performed to evaluate the expression of circRNAs in human bone marrow-derived MSCs (hMSCs) induced to undergo chondrogenesis from day 0 to day 21. The regulatory and functional roles of exosomal circRNA_0001236 were examined on day 21 after inducing chondrogenesis in hMSCs and were validated in vitro and in vivo. The downstream target of circRNA_0001236 was also explored in vitro and in vivo using bioinformatics analyses. A luciferase reporter assay was used to evaluate the interaction between circRNA_0001236 and miR-3677-3p as well as the target gene sex-determining region Y-box 9 (Sox9). The function and mechanism of exosomal circRNA_0001236 in OA were explored in the DMM mouse model. Upregulation of exosomal circRNA_0001236 enhanced the expression of Col2a1 and Sox9 but inhibited that of MMP13 in hMSCs induced to undergo chondrogenesis. Moreover, circRNA_0001236 acted as an miR-3677-3p sponge and functioned in human chondrocytes via targeting miR-3677-3p and Sox9. Intra-articular injection of exosomal circRNA_0001236 attenuated OA in the DMM mouse model. Our results reveal an important role for a novel exosomal circRNA_0001236 in chondrogenic differentiation. Overexpression of exosomal circRNA_0001236 promoted cartilage-specific gene and protein expression through the miR-3677-3p/Sox9 axis. Thus, circRNA_0001236-overexpressing exosomes may alleviate cartilage degradation, suppressing OA progression and enhancing cartilage repair. Our findings provide a potentially effective therapeutic strategy for treating OA. The online version contains supplementary material available at 10.1186/s13287-021-02431-5.
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DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
28.3
作者：
Nandakumar, Ramya;Tschismarov, Roland;Paludan, Soren R.
通讯作者：
Paludan, Soren R.
CircRNA hsa_circ_0074834 通过充当 miR-942-5p 的 ceRNA 促进骨间充质干细胞 (BMSC) 中的成骨-血管生成偶联过程
影响因子：
9
作者：
Ouyang, Zhengxiao;Tan, Tingting;Liu, Tang
通讯作者：
Liu, Tang
DOI：
10.1038/nri3622
发表时间：
2014-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
circTP63 作为 ceRNA 通过上调 FOXM1 促进肺鳞状细胞癌进展
影响因子：
16.6
作者：
Cheng, Zhuoan;Yu, Chengtao;Qin, Wenxin
通讯作者：
Qin, Wenxin