Lnc<scp>RNA</scp>‐<scp>H</scp>19 <scp>M</scp>odulates <scp>W</scp>nt/β‐catenin Signaling by <scp>T</scp>argeting <scp>D</scp>kk4 in <scp>H</scp>indlimb Unloaded Rat

Li, Bing; Li, Jun; Zhao, Jie; Ma, Jianxiong; Jia, Haobo; Zhang, Yang; Xing, Guosheng; Ma, Xiaofang

doi:10.1111/os.12321

Cited by 46 publications

(43 citation statements)

References 37 publications

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“…[24][25][26][27] Importantly, although the roles of lncRNAs in the process of osteogenesis have been widely reported, [28][29][30] only a few studies have shown that lncRNAs are involved in the occurrence and development of unloading-induced bone loss. 31,32 In the present study, we found that lncRNA OGRU is downregulated during unloading and upregulated during osteoblast differentiation. OGRU overexpression promoted osteoblast activity and matrix mineralization under normal loading and attenuated the suppression of MC3T3-E1 cell differentiation by unloading conditions in vitro.…”

Section: Introductionsupporting

confidence: 59%

“…46 In particular, the lncRNA H19 (H19) is a key regulator of osteoblast function and is involved in the development of disuse osteoporosis, suggesting that lncRNAs may play a key role in unloading-induced bone loss. 31,32,47,48 Our previous work found many lncRNAs that are significantly differentially expressed in MC3T3-E1 cells under clinorotation unloading condition for 48 h. Further exploration identified a novel unloading-sensitive lncRNA, OGRU, which promotes the osteoblast activity and matrix mineralization and attenuates the osteogenic impairment of MC3T3-E1 cells induced by clinorotation unloading. To further determine whether OGRU can rescue unloading-induced bone loss in vivo, pcDNA3.1(+)-OGRU was delivered via (DSS) 6 -liposomes to bone formation surfaces in HLU mice.…”

Section: Discussionmentioning

confidence: 91%

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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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Section: Introductionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 91%

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

Wang

et al. 2019

Preprint

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“…Intersections between various mechanical stimuli and H19 expression have been previously shown, including in a pressure overload model of cardiac hypertrophy, a hindlimb unloading model of osteoporosis, and tension induced osteogenesis. 14,19,30 In these studies, strain correlated with expression of H19. Similarly, H19 is known to be upregulated in calcific aortic valve disease, a pathology characterized by increased valvular strain which augments valve calcification.…”

Section: Discussionmentioning

confidence: 98%

Cyclic Strain Promotes H19 Expression and Vascular Tube Formation in iPSC-Derived Endothelial Cells

Roest

Merryman

2020

Cel. Mol. Bioeng.

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Introduction-Induced pluripotent stem cell (iPSC)-derived endothelial cells (ECs) have the potential for therapeutic application in several cardiovascular diseases. Mechanical strain is known to regulate EC behavior and stem cell differentiation and may play a role in directing EC differentiation of iPSCs. H19, a long non-coding RNA (lncRNA), is known to affect ECs in several mechanically relevant pathologies and may play a role in this process as well. Therefore, we investigated expression changes of H19 resulting from mechanical stimulation during EC differentiation, as well as functional effects on EC tube formation. Methods-iPSCs were subjected to 5% cyclic mechanical strain during EC differentiation. RT-PCR and flow cytometry were used to assess changes in mesoderm differentiation and gene expression in the final ECs as a result of strain. Functional outcomes of mechanically differentiated ECs were assessed with a tube formation assay and changes in H19. H19 was also overexpressed in human umbilical vein endothelial cells (HUVECs) to assess its role in non-H19expressing ECs. Results-Mechanical strain promoted mesoderm differentiation, marked by increased expression of brachyury 24 h after initiation of differentiation. Strain also increased expression of H19, CD31, VE-cadherin, and VEGFR2 in differentiated ECs. Strain-differentiated ECs formed tube networks with higher junction and endpoint density than statically-differentiated ECs. Overexpression of H19 in HUVECs resulted in similar patterns of tube formation. Conclusions-H19 expression is increased by mechanical strain and promotes tube branching in iPSC-derived ECs.

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“…Among confirmed osteogenesis‐related lncRNAs, H19 in cell growth and differentiation has been extensively studied. In recent years, several lines of evidence showed its role in the osteogenic differentiation of MSCs (Huang et al, 2015; Li et al, 2017; Liang et al, 2016; Liao et al, 2017). It is noteworthy that lncRNA H19 might involve in the process of osteogenic differentiation of MSCs via Wnt/β‐catenin pathway (Liang et al, 2016).…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA expression profiles during the NEL‐like 1 protein–induced osteogenic differentiation

Xia

Cen

et al. 2020

Journal Cellular Physiology

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Long noncoding RNAs (lncRNAs) are important modulators of mesenchymal stem cells (MSCs) in cellular differentiation. However, the regulatory mechanisms of lncRNAs in NEL-like 1 (NELL-1)-induced osteogenic differentiation of human adipose-derived stem cells remain elusive. Expression profiles of lncRNAs and messenger RNAs during NELL-1induced osteogenesis were obtained using high-throughput sequencing. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and gene coexpression networks were performed. We identified 323 statistically differentially expressed lncRNAs during osteogenesis and NELL-1-induced osteogenesis, and three lncRNAs (ENST00000602964, ENST00000326734, and TCONS_00006792) were identified as core regulators. Hedgehog pathway markers, including IHH and GLI1, were downregulated, while the antagonists of this pathway (GLI3 and HHIP) were upregulated during NELL-1-induced osteogenesis. In this process, the antagonist of Wnt, SFRP1, was downregulated. According to the analysis, we speculated that lncRNAs played important roles in NELL-1-induced osteogenesis via the crosstalk between Hedgehog and Wnt pathways.

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LncRNA‐H19 Modulates Wnt/β‐catenin Signaling by Targeting Dkk4 in Hindlimb Unloaded Rat

Abstract: Our findings demonstrated that low expression of H19, induced by mechanical unloading, leads to development of DOP through inhibition of Wnt signaling by promoting Dkk4 expression.

Cited by 46 publications

References 37 publications

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

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

Cyclic Strain Promotes H19 Expression and Vascular Tube Formation in iPSC-Derived Endothelial Cells

Long noncoding RNA expression profiles during the NEL‐like 1 protein–induced osteogenic differentiation

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