H19 and Foxc2 synergistically promotes osteogenic differentiation of BMSCs via Wnt‐β‐catenin pathway

Zhou, Ping; Liu, Ying; Di, Ruolin; Yang, Yudi; Meng, Songyan; Song, Frank M.; Ma, Liang

doi:10.1002/jcp.28060

Cited by 45 publications

(28 citation statements)

References 26 publications

(40 reference statements)

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“…It has been found that H19 downregulation modulated osteogenic differentiation of BMSCs from ovariectomized mouse, which suggested an important role of H19 in postmenopausal osteoporosis [26]. In the present study, we observed a significant decrease of H19 expression in postmenopausal osteoporosis patients and in BMP-2 induced BMSCs compared with controls, which was consistent with a former study [26]. And more importantly, our results indicated that H19 overexpression downregulated miR-19b-3p expression in BMSCs.…”

Section: Discussionsupporting

confidence: 92%

“…LncRNA H19 has been addressed in various cancers as an oncogene, and regulated cell proliferation, apoptosis and migration [25]. It has been found that H19 downregulation modulated osteogenic differentiation of BMSCs from ovariectomized mouse, which suggested an important role of H19 in postmenopausal osteoporosis [26]. In the present study, we observed a significant decrease of H19 expression in postmenopausal osteoporosis patients and in BMP-2 induced BMSCs compared with controls, which was consistent with a former study [26].…”

Section: Discussionsupporting

confidence: 92%

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MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

2020

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Background: To investigated the role of miR-19b-3p in regulating bone marrow mesenchymal stem cell (BMSC) proliferation and osteoblast differentiation. Methods: The expression of miR-19b-3p and lncRNA H19 were measured in postmenopausal osteoporosis patients and BMP-22 induced BMSCs using qRT-PCR. MiR-19b-3p mimic or inhibitor was transfected into BMP-2 induced BMSCs. Cell proliferation was measured by BrdU method. Protein expression of RUNX2 and COL1A1 were measured by western blot. PcDNA3.1-lncRNA H19 with or without miR-19b-3p mimic was transfected into BMP-2 induced BMSCs. Results: The expression of miR-19b-3p was significantly up-regulated in postmenopausal osteoporosis patients and BMP-2 induced BMSCs. MiR-19b-3p overexpression dramatically elevated, while miR-19b-3p inhibition decreased cell proliferation of BMSCs. Additionally, protein expression levels of RUNX2 and COL1A1, as well as ALP activity were significantly promoted by miR-19b-3p mimic transfection and inhibited by miR-19b-3p inhibitor transfection. LncRNA H19 was obviously down-regulated in postmenopausal osteoporosis patients. H19 overexpression significantly decreased cell proliferation and differentiation by down-regulating miR-19b-3p. Moreover, the expression of miR-19b-3p was inhibited, while H19 elvated in 17β-estradiol (E2) treated BMSCs in a dose-dependent manner. Conclusion: These data were the first to reveal the critical role of H19/miR-19b-3p in postmenopausal osteoporosis, and provided a new therapeutic target for OP.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 92%

MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

2020

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“…Although Morusin has the ability to effectively advance osteogenic differentiation of BMSCs, its underlying mechanism remains unclear. As confirmed by previous studies, Wnt/β-catenin signaling pathway is a great mediator of BMSCs differentiation into osteoblasts [37][38][39]. Therefore, we studied the function of Wnt/β-catenin signaling pathway in the osteogenesis of BMSCs treated by Morusin.…”

Section: Discussionmentioning

confidence: 52%

Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model

et al. 2021

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Background Osteoporosis (OP) is a metabolic bone disease due to the imbalance of osteogenesis and bone resorption, in which, bone marrow mesenchymal stem cells (BMSCs) have a significant effect as the seed cells. Recent research has shown the function of Morusin on inhibiting osteoclast differentiation in vitro. However, whether Morusin can regulate the osteogenic differentiation in addition to the proliferation of BMSCs remains unclear. Methods BMSCs were isolated from 4-week-old Wistar rats and then treated with different concentrations of Morusin for 3, 5, 7, and 14 days. The proliferation of BMSCs was detected by MTT assay. The effect of Morusin on osteogenic differentiation of BMSCs was detected by RT-qPCR, Western blotting, ALP, and Alizarin Red staining. The effect of Morusin on Wnt/β-catenin signaling pathway was analyzed by RT-qPCR, Western blotting, and immunofluorescence. Finally, in the ovariectomy-induced osteoporosis model, the anti-osteoporosis activity of Morusin was determined by micro-CT, HE, and immunohistochemistry. Results The results showed the function of 2.5–10 μM Morusin in the promotion of the proliferation in addition to osteogenic differentiation of BMSCs. Moreover, it also has an impact in activating the Wnt/β-catenin signaling pathway via inhibition of β-catenin phosphorylation as well as promotion of its nuclear translocation. Upon Dickkopf-related protein-1 (DKK-1, an inhibitor of the Wnt/β-catenin signaling pathway) was added to the Morusin, Morusin had a decreased stimulatory osteogenic effect on BMSCs. Finally, in the rat OP model, we found that Morusin could also exert anti-osteoporosis activity in vivo. Conclusions This study indicates the ability of Morusin in the promotion of osteogenic differentiation of BMSCs via the activation of Wnt/β-catenin signaling pathway and also shows the potential of Morusin to be an agent for osteoporosis treatment.

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“…Among LncRNAs, H19 has been addressed in various cancers as an oncogene, and regulated cell proliferation, apoptosis and migration [64]. It has been found that H19 down-regulation modulated osteogenic differentiation of BMSCs from ovariectomized mouse, which suggested an important role of H19 in postmenopausal osteoporosis [65]. LncRNA H19 also mediates mechanical tension-induced osteogenesis of BMMSCs via FAK by sponging miR-138 [32].…”

Section: Discussionmentioning

confidence: 99%

LncRNA H19 from T-Regulatory-Cell-Derived Exosomes Sponges miR-154-5p to Promote Osteogenic Differentiation of BMMSCs Through Upregulating POSTN

Zhang

Liu

et al. 2021

Preprint

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Background: Mesenchymal stem cells (MSCs) can play an important role in anti-inflammatory function because it can induce Treg cells formation. Recent studies have confirmed that Tregs can release exosomes and induce immune tolerance as important immune cells. Thus, to clarify the function and regulatory mechanism of Treg cells-derived exosomes on osteogenic differentiation of BMMSCs is very important.Methods: CD4+ T cells isolated from mouse spleens were induced into CD4+ Foxp3+ Treg cells and co-cultured with BMMSCs. Then we isolated exosomes derived from Treg cells and tracked the exosomes using fluorescent labeling PKH67.Starbase, miRWalk, targetscan, bioinformatics analysis and functional complementation experiments to find relative lncRNA-miRNAs which involed in osteogenic differentiation of BMMSCs.Results: We found that exosomes derived from Tregs could enter BMMSCs and the expression of osteoblast-related genes were significantly up-regulated compared to the BMMSCs co-cultured with naïve T cells. LncRNA H19 from Tregs-derived exosomes could affect the osteogenic differentiation of BMMSCs in vitro by regulating POSTN expression via sponge miR-154-5p.Conclusions: This study demonstrated that important role of exosomes from Tregs in regulating osteogenic differentiation of BMMSCs. lncRNA H19 from Tregs-derived exosomes plays a positive regulatory role in osteogenic differentiation of BMMSCs through miR-154-5p/POSTN axis. It might has important clinical implications for inflammatory diseases and exosomes released from Tregs could be used as a new type of immunoregulation reagent for the treatment of periodontitis.

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H19 and Foxc2 synergistically promotes osteogenic differentiation of BMSCs via Wnt‐β‐catenin pathway

Cited by 45 publications

References 26 publications

MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

MicroRNA-19b-3p promotes cell proliferation and osteogenic differentiation of BMSCs by interacting with lncRNA H19

Morusin induces osteogenic differentiation of bone marrow mesenchymal stem cells by canonical Wnt/β-catenin pathway and prevents bone loss in an ovariectomized rat model

LncRNA H19 from T-Regulatory-Cell-Derived Exosomes Sponges miR-154-5p to Promote Osteogenic Differentiation of BMMSCs Through Upregulating POSTN

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