MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

Wang, Yixuan; Wang, Ke; Hu, Zebing; Zhou, Hua; Zhang, Lijun; Wang, Han; Li, Gaozhi; Zhang, Shu; Cao, Xinsheng; Shi, Fei

doi:10.1038/s41419-018-1153-1

Cited by 68 publications

(64 citation statements)

References 46 publications

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“…Our previous experiments confirmed that lncRNA ODSM and miR-139-3p interact with and repress each other 27 . By using the online lncRNA location prediction software lncLocator (http://www.csbio.sjtu.edu.cn/bioinf/ lncLocator/) and cell fractionation followed by quantitative reverse transcription polymerase chain reaction (qRT-PCR), we identified that lncRNA ODSM expression was located in the cytoplasm and nuclei of cells (Supplementary Fig.…”

Section: Lncrna Odsm Interacts With Mir-139-3p To Regulate Elk1 Expresupporting

confidence: 77%

“…The regulation of ELK1 by miR-139-3p relies on the 3′-UTR region of ELK1, so if the regulatory effect of the lncRNA ODSM on ELK1 depends on competitive binding to miR-139-3p, then the lncRNA ODSM should also have a regulatory effect on the 3′-UTR region of ELK1. We constructed luciferase reporter vectors containing the ELK1 3′-UTR sequence and the lncRNA ODSM sequence with a wild-type (pEX-ODSM WT) or mutated miR-139-3p binding site (pEX-ODSM MUT) as previously reported 27 , and we then transfected these vectors into cells. Overexpression of the lncRNA ODSM, but not pEX-ODSM MUT, partly blocked the mimic-139-induced reduction in luciferase activity of the ELK1 reporter vector.…”

Section: Lncrna Odsm Interacts With Mir-139-3p To Regulate Elk1 Exprementioning

confidence: 99%

“…MiR-139-3p alleviated the effect of MG unloading on differentiation and apoptosis in MC3T3-E1 cells, through its target gene ELK1 (ref. 27 ). Based on the above results, we aimed to verify whether intervening with lncRNA ODSM expression can affect osteoblast functions and bone formation in a mechanical unloading environment in vitro or in vivo.…”

Section: Introductionmentioning

confidence: 99%

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Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

Wang

Zhang

et al. 2020

Cell Death Dis

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Ameliorating bone loss caused by mechanical unloading is a substantial clinical challenge, and the role of noncoding RNAs in this process has attracted increasing attention. In this study, we found that the long noncoding RNA osteoblast differentiation-related lncRNA under simulated microgravity (lncRNA ODSM) could inhibit osteoblast apoptosis and promote osteoblast mineralization in vitro. The increased expression level of the lncRNA ODSM partially reduced apoptosis and promoted differentiation in MC3T3-E1 cells under microgravity unloading conditions, and the effect was partially dependent on miR-139-3p. LncRNA ODSM supplementation in hindlimb-unloaded mice caused a decrease in the number of apoptotic cells in bone tissue and an increase in osteoblast activity. Furthermore, targeted overexpression of the lncRNA ODSM in osteoblasts partially reversed bone loss induced by mechanical unloading at the microstructural and biomechanical levels. These findings are the first to suggest the potential value of the lncRNA ODSM in osteoporosis therapy and the treatment of pathological osteopenia.

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Section: Lncrna Odsm Interacts With Mir-139-3p To Regulate Elk1 Expresupporting

confidence: 77%

Section: Lncrna Odsm Interacts With Mir-139-3p To Regulate Elk1 Exprementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

Wang

Zhang

et al. 2020

Cell Death Dis

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“…A 2D clinostat (developed by the China Astronaut Research and Training Center, Beijing, China) was selected to simulate the unloading environment in vitro, and related experiments were performed according to the procedure described previously. 13,65 Briefly, MC3T3-E1 cells were seeded in 25-cm 2 culture flasks at a density of 5×10 5 cells per flask. After cell adherence, the culture flasks were filled with osteogenic medium, ensuring that air bubbles were removed.…”

Section: Clinorotationmentioning

confidence: 99%

“…6 HLU mice, an established model used to simulate skeletal unloading, show irreversible bone loss via the inhibition of bone formation and the promotion of bone resorption. 5,[7][8][9] In vitro experiments in ground-based facilities for simulating microgravity unloading, such as 2D clinostat, random positioning machine (RPM), rotating wall vessel (RWV) bioreactor and magnetic levitator, indicated that the dysfunction of osteoblasts caused by unloading can disturb their ability to translate mechanical loading into biochemical signals, which can partly explain the occurrence of unloading-induced bone loss, [10][11][12][13] and many intracellular signaling pathways have been reported to participate in this complex process. 5,8,14 To further understand the pathophysiology of unloading-induced bone loss and identify new biological targets, we selected 2D clinorotation and HLU models for simulating unloading conditions in vitro and in vivo.…”

Section: Introductionmentioning

confidence: 99%

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Wang

et al. 2019

Preprint

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Although the underlying molecular mechanism of unloading-induced bone loss has been broadly elucidated, the pathophysiological role of long noncoding RNAs (lncRNAs) in this process is unknown. Here, we identified a novel lncRNA, OGRU, a 1816-nucleotide transcript with significantly decreased levels in bone specimens from hindlimb-unloaded mice and in MC3T3-E1 cells under clinorotation unloading conditions. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading conditions and attenuated the suppression of MC3T3-E1 cell differentiation induced by clinorotation unloading. Furthermore, this study found that supplementation of pcDNA3.1(+)-OGRU via (DSS) 6 -liposome delivery to the bone formation surfaces of hindlimb-unloaded (HLU) mice partially alleviated unloading-induced bone loss. Mechanistic investigations demonstrated that OGRU can function as a competing endogenous RNA (ceRNA) to facilitate the protein expression of Hoxa10 by competitively binding miR-320-3p and subsequently promote osteoblast differentiation and bone formation. Taken together, the results of our study provide the first clarification of the role of the OGRU in unloading-induced bone loss through the miR-320-3p/Hoxa10 axis, suggesting an efficient anabolic strategy for osteoporosis treatment.

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Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

Born

Harmon

Jay

2020

Bioengineering & Transla Med

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Both extracellular vesicles (EVs) and long noncoding RNAs (lncRNAs) have been increasingly investigated as biomarkers, pathophysiological mediators, and potential therapeutics. While these two entities have often been studied separately, there are increasing reports of EV-associated lncRNA activity in processes such as oncogenesis as well as tissue repair and regeneration. Given the powerful nature and emerging translational impact of other noncoding RNAs such as microRNA (miRNA) and small interfering RNA, lncRNA therapeutics may represent a new frontier. While EVs are natural vehicles that transport and protect lncRNAs physiologically, they can also be engineered for enhanced cargo loading and therapeutic properties. In this review, we will summarize the activity of lncRNAs relevant to both tissue repair and cancer treatment and discuss the role of EVs in enabling the potential of lncRNA therapeutics. K E Y W O R D S exosomes, extracellular vesicles, lncRNA, microparticles, microvesicles lncRNAs play diverse regulatory roles in normal physiological processes. Thus, delivery of lncRNAs via EVs may help in the treatment Abbreviations: CRCs, colorectal carcinoma cells; EVs, extracellular vesicles; hAD-MSCs, human adipose-derived mesenchymal stem cells; HCAECs, human coronary artery endothelial cells; HCC, hepatocellular carcinoma cell; HDFs, human dermal fibroblasts; HDMECs, human dermal microvascular endothelial cells; lncRNA, long noncoding RNA; miRNA, microRNA; SCCs, squamous carcinoma cells.

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MicroRNA-139-3p regulates osteoblast differentiation and apoptosis by targeting ELK1 and interacting with long noncoding RNA ODSM

Cited by 68 publications

References 46 publications

Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

Targeted overexpression of the long noncoding RNA ODSM can regulate osteoblast function in vitro and in vivo

Bone-targeted lncRNA OGRU alleviates unloading-induced bone loss via miR-320-3p/Hoxa10 axis

Therapeutic potential of extracellular vesicle‐associated long noncoding RNA

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