CircPVT1 up-regulation attenuates steroid-induced osteonecrosis of the femoral head through regulating miR-21-5p-mediated Smad7/TGFβ signalling pathway.
CircPVT1 up-regulation attenuates steroid-induced osteonecrosis of the femoral head through regulating miR-21-5p-mediated Smad7/TGFβ signalling pathway.
复制标题
DOI：
10.1111/jcmm.16294
复制
发表时间：
2021-05
影响因子：
5.3
通讯作者：
Zhang G
中科院分区：
文献类型：
--
作者：
Hao Y;Lu C;Zhang B;Xu Z;Guo H;Zhang G
激素性股骨头坏死（SIONFH）是皮质类固醇治疗后的常见疾病。目前，我们旨在探讨环状RNA (circ) PVT1在SIONFH大鼠中的功能及其机制。采用糖皮质激素（GC）对SD大鼠和骨髓间充质干细胞（BMSCs）分别进行体外和体内处理，构建SIONFH模型。采用血红素-伊红（HE）染色和免疫组化（IHC）检测SIONFH大鼠股骨头病理损伤情况。检测骨髓间充质干细胞的成骨分化、增殖和凋亡情况。Western blot检测Smad7、Bax、Bcl2和Smad2/3。circPVT1和miR‐21‐5p的潜在靶点分别通过荧光素酶报告基因实验和RNA拉下实验进行了验证。我们发现CircPVT1在SIONFH大鼠股骨头和GC处理的骨髓间充质干细胞中减少，而miR - 21 - 5p明显上调。过表达的circPVT1可减轻GC诱导的骨髓间充质干细胞的凋亡和细胞活力抑制，而miR - 21 - 5p上调则具有相反的作用。此外，体内实验证实，上调circPVT1通过抑制细胞凋亡抑制SIONFH大鼠的骨坏死。从机制上讲，circPVT1作为miR - 21 - 5p的ceRNA，靶向Smad7的3'非翻译区。CircPVT1通过抑制miR - 21 - 5p增强Smad7和减轻GC激活TGFβ/Smad2/3通路。综上所述，CircPVT1通过调节miR‐21‐5p‐介导的Smad7/TGFβ途径对SIONFH发挥保护作用。
Steroid‐induced osteonecrosis of the femoral head (SIONFH) has been a common disease following corticosteroid therapy. Presently, we aim to explore the functions of circular RNA (circ) PVT1 in SIONFH rats and the underlying mechanism. Glucocorticoid (GC) was used to treat SD rats and bone marrow‐derived mesenchymal stem cells (BMSCs) to construct SIONFH model in vitro and in vivo, respectively. The pathological injury of the femoral head in the SIONFH rats was detected via haematoxylin‐eosin (HE) staining and immunohistochemistry (IHC). The osteogenic differentiation, proliferation and apoptosis of BMSCs were detected. Western blot was used to detect Smad7, Bax, Bcl2 and Smad2/3. The potential targets of circPVT1 and miR‐21‐5p were validated through luciferase reporter gene assay and RNA pull‐down assay, respectively. We found that CircPVT1 was decreased in the femoral head of SIONFH rats and GC‐treated BMSCs, while miR‐21‐5p was markedly up‐regulated. Overexpressed circPVT1 attenuated the apoptosis and cell viability inhibition of BMSCs induced by GC, while miR‐21‐5p up‐regulation had the opposite effects. What's more, the in vivo experiments confirmed that up‐regulating circPVT1 repressed osteonecrosis in SIONFH rats through repressing apoptosis. Mechanistically, circPVT1 functioned as a ceRNA of miR‐21‐5p, which targeted at the 3'untranslated region of Smad7. CircPVT1 enhancing Smad7 and mitigating GC activated TGFβ/Smad2/3 pathway through inhibiting miR‐21‐5p. In conclusion, CircPVT1 exerts protective effects against SIONFH via modulating miR‐21‐5p‐mediated Smad7/TGFβ pathway.
登录
查看更多内容
影响因子：
5.3
作者：
Hao Y;Lu C;Zhang B;Xu Z;Guo H;Zhang G
通讯作者：
Zhang G
影响因子：
13.8
作者：
Macias, Maria J.;Martin-Malpartida, Pau;Massague, Joan
通讯作者：
Massague, Joan
DOI：
10.1111/1440-1681.13273
发表时间：
2020-02-27
影响因子：
2.9
作者：
Li, Yong;Shi, Haitao;Wang, Yan
通讯作者：
Wang, Yan
影响因子：
9
作者：
Gao, Xiao;Xiong, Ye;Li, Gang
通讯作者：
Li, Gang
DOI：
10.1016/j.msec.2019.02.072
发表时间：
2019-06-01
影响因子：
7.9
作者：
Liu, Baoyi;Yang, Fan;Zhao, Dewei
通讯作者：
Zhao, Dewei