CircUSP45 通过海绵吸附 miR-127-5p 抑制糖皮质激素诱导的股骨头坏死中的成骨作用：实验研究。
CircUSP45 inhibited osteogenesis in glucocorticoid-induced osteonecrosis of femoral head by sponging miR-127-5p through PTEN/AKT signal pathway: Experimental studies.
机构信息
Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, 300052, People's Republic of China.
Tianjin Hospital, Tianjin, 300211, People's Republic of China.
出版信息
Biochem Biophys Res Commun. 2019 Jan 29;509(1):255-261. doi: 10.1016/j.bbrc.2018.12.116. Epub 2018 Dec 20.
PURPOSE
large doses of glucocorticoids (GCs) are the most common cause of glucocorticoid-induced osteonecrosis of femoral head (GIONFH). Although awareness of GIONFH among patients with GCs history has increased over recent years, several studies indicate that its mechanism remains unclear.
METHODS
To evaluate the function of circUSP45 in GIONFH, femoral heads in GIONFH patients or femoral heads in fracture patients were collected. In vitro, RT-PCR, FISH, RNA pull down and Western blotting assay were used to evaluate the function of circUSP45. In addition, we also verified the effects of circUSP45 on osteogenesis using alizarin red staining. In vivo, we used HE staining and microCT analysis to evaluate the bone mass. Moreover, the mechanism of circUSP45 regulating osteogenesis through the miR-127-5p/PTEN/AKT pathway was also investigated.
RESULTS
The results showed that expression of circUSP45 increased in GIONFH patients. The overexpression of circUSP45 decreases osteogenic gene expression and inhibits the proliferation of BMSCs. Furthermore, circUSP45 was located mainly in the cytoplasm and directly interacted with miR-127-5p. MiR-127-5p acts with its targets PTEN to regulate the osteogenesis. MicroCT and HE staining verify the function of circUSP45 in GIONFH rat model.
CONCLUSION
CircUSP45 decreases osteogenesis in bone GIONFH by sponging miR-127-5p through PTEN/AKT signal pathway.
目的
大剂量糖皮质激素（GCs）是引起股骨头坏死（GIONFH）的最常见原因。尽管近年来患者对 GCs 病史的 GIONFH 认识有所提高，但多项研究表明其机制仍不清楚。
方法
为了评估 circUSP45 在 GIONFH 中的作用，收集了 GIONFH 患者的股骨头或骨折患者的股骨头。在体外，通过 RT-PCR、FISH、RNA 下拉和 Western blot 分析评估 circUSP45 的功能。此外，我们还通过茜素红染色验证了 circUSP45 对成骨作用的影响。在体内，我们使用 HE 染色和 microCT 分析来评估骨量。此外，还研究了 circUSP45 通过 miR-127-5p/PTEN/AKT 通路调节成骨作用的机制。
结果
结果表明，circUSP45 在 GIONFH 患者中的表达增加。circUSP45 的过表达降低成骨基因的表达并抑制 BMSCs 的增殖。此外，circUSP45 主要位于细胞质中，并与 miR-127-5p 直接相互作用。miR-127-5p 与其靶标 PTEN 结合，调节成骨作用。MicroCT 和 HE 染色验证了 circUSP45 在 GIONFH 大鼠模型中的作用。
结论
circUSP45 通过 PTEN/AKT 信号通路海绵吸附 miR-127-5p 减少骨 GIONFH 中的成骨作用。
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