Long noncoding RNA TRG-AS1 protects against glucocorticoid-induced osteoporosis in a rat model by regulating miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.

IF 4.3 3区生物学

Human Cell Pub Date : 2022-09-01 Epub Date: 2022-07-07 DOI:10.1007/s13577-022-00741-1

Wen Liu, Guojuan Li, Jing Li, Wei Chen

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引用次数: 4

Abstract

The long-term treatment of glucocorticoids is a common cause of osteoporosis (OP). This study concentrated on inquiring into the regulatory role and potential mechanisms of TRG-AS1 on dexamethasone (Dex)-induced OP in rats. We adopted Dex to treat rat osteoblasts and rats to simulate in-vitro and in-vivo OP models, respectively. Gain-of-function assays of TRG-AS1, miR-802 and CAB39 were constructed in rat osteoblasts to make certain the influence of TRG-AS1, miR-802 and CAB39 on differentiation, proliferation and apoptosis of rat osteoblasts. TRG-AS1 and CAB39 were down-regulated in the Dex-induced OP model in rats, in contrast to miR-802. Overexpression of TRG-AS1 restrained Dex-induced inhibition of osteogenic differentiation, promoted CAB39/AMPK/SIRT-1 and inhibited NF-κB, while overexpression of miR-802 bridled the inhibitory effect of TRG-AS1 on OP. miR-802 was targeted by TRG-AS1, and inhibited CAB39. Inhibition of either AMPK or SIRT-1 abated the osteogenic differentiation-promoting effect of CAB39. Animal experiments displayed that overexpressing TRG-AS1 alleviated Dex-induced OP in rats. In conclusion, up-regulation of TRG-AS1 protected against glucocorticoid-induced OP in rats by modulating the miR-802-mediated CAB39/AMPK/SIRT-1/NF-κB axis.

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在大鼠模型中，长链非编码RNA TRG-AS1通过调节mir -802介导的CAB39/AMPK/SIRT-1/NF-κB轴，保护糖皮质激素诱导的骨质疏松症。

糖皮质激素的长期治疗是骨质疏松症(OP)的常见原因。本研究主要探讨TRG-AS1对地塞米松(Dex)诱导大鼠OP的调控作用及其可能机制。我们采用Dex分别处理大鼠成骨细胞和大鼠体外和体内模拟OP模型。在大鼠成骨细胞中构建TRG-AS1、miR-802和CAB39的功能获得实验，以确定TRG-AS1、miR-802和CAB39对大鼠成骨细胞分化、增殖和凋亡的影响。与miR-802相比，TRG-AS1和CAB39在dex诱导的大鼠OP模型中下调。TRG-AS1过表达抑制了dex诱导的成骨分化抑制，促进了CAB39/AMPK/SIRT-1，抑制了NF-κB，而miR-802过表达抑制了TRG-AS1对op的抑制作用，miR-802被TRG-AS1靶向，抑制了CAB39。抑制AMPK或SIRT-1均可减弱CAB39促进成骨分化的作用。动物实验表明，过表达TRG-AS1可减轻dex诱导的大鼠OP。综上所述，上调TRG-AS1通过调节mir -802介导的CAB39/AMPK/SIRT-1/NF-κB轴，对糖皮质激素诱导的大鼠OP具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Human Cell 生物-细胞生物学

CiteScore

6.60

自引率

2.30%

发文量

176

期刊介绍： Human Cell is the official English-language journal of the Japan Human Cell Society. The journal serves as a forum for international research on all aspects of the human cell, encompassing not only cell biology but also pathology, cytology, and oncology, including clinical oncology. Embryonic stem cells derived from animals, regenerative medicine using animal cells, and experimental animal models with implications for human diseases are covered as well. Submissions in any of the following categories will be considered: Research Articles, Cell Lines, Rapid Communications, Reviews, and Letters to the Editor. A brief clinical case report focusing on cellular responses to pathological insults in human studies may also be submitted as a Letter to the Editor in a concise and short format. Not only basic scientists but also gynecologists, oncologists, and other clinical scientists are welcome to submit work expressing new ideas or research using human cells.