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流体切应力通过 lncRNA TUG1/miR-34a/FGFR1 轴调节成骨细胞增殖和凋亡。

Fluid shear stress regulates osteoblast proliferation and apoptosis via the lncRNA TUG1/miR-34a/FGFR1 axis.

机构信息

Department of Orthopaedics, Lanzhou University Second Hospital, Lanzhou, Gansu, China.

Orthopaedics Key Laboratory of Gansu Province, Lanzhou, Gansu, China.

出版信息

J Cell Mol Med. 2021 Sep;25(18):8734-8747. doi: 10.1111/jcmm.16829. Epub 2021 Aug 5.

DOI:10.1111/jcmm.16829
PMID:34350720
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8435422/
Abstract

LncRNAs and microRNAs play critical roles in osteoblast differentiation and bone formation. However, their exact roles in osteoblasts under fluid shear stress (FSS) and the possible mechanisms remain unclear. The aim of this study was to explore whether and how miR-34a regulates osteoblast proliferation and apoptosis under FSS. In this study, FSS down-regulated miR-34a levels of MC3T3-E1 cells. MiR-34a up-regulation attenuated FSS-induced promotion of proliferation and suppression of apoptosis. Luciferase reporter assay revealed that miR-34a directly targeted FGFR1. Moreover, miR-34a regulated osteoblast proliferation and apoptosis via FGFR1. Further, we validated that lncRNA TUG1 acted as a competing endogenous RNA (ceRNA) to interact with miR-34a and up-regulate FGFR1 protein expression. Furthermore, lncRNA TUG1 could promote proliferation and inhibit apoptosis. Taken together, our study revealed the key role of the lncRNA TUG1/miR-34a/FGFR1 axis in FSS-regulated osteoblast proliferation and apoptosis and may provide potential therapeutic targets for osteoporosis.

摘要

长链非编码 RNA 和 microRNAs 在成骨细胞分化和骨形成中发挥关键作用。然而，它们在流体切应力 (FSS) 下成骨细胞中的确切作用以及可能的机制尚不清楚。本研究旨在探讨 miR-34a 是否以及如何在 FSS 下调节成骨细胞的增殖和凋亡。在这项研究中，FSS 下调了 MC3T3-E1 细胞中的 miR-34a 水平。miR-34a 的上调减弱了 FSS 诱导的增殖促进和凋亡抑制。荧光素酶报告基因检测显示，miR-34a 可直接靶向 FGFR1。此外，miR-34a 通过 FGFR1 调节成骨细胞的增殖和凋亡。此外，我们验证了 lncRNA TUG1 作为竞争性内源性 RNA (ceRNA) 与 miR-34a 相互作用并上调 FGFR1 蛋白表达。此外，lncRNA TUG1 可促进增殖并抑制凋亡。综上所述，我们的研究揭示了 lncRNA TUG1/miR-34a/FGFR1 轴在 FSS 调节成骨细胞增殖和凋亡中的关键作用，并可为骨质疏松症提供潜在的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1191/8435422/a1a730105a68/JCMM-25-8734-g004.jpg
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