LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p

Wang, Qiujun; Liu, Ying; Zhang, Yuanxia; Ma, Liang; Lin, Lin; Meng, Jia; Jiang, Lihong; Wang, Liping; Zhou, Ping; Zhang, Yina

doi:10.1016/j.biopha.2017.02.090

Cited by 178 publications

(147 citation statements)

References 20 publications

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“…LncRNA-DANCR has been reported to be a potential biomarker for osteoporosis [9]. Another lncRNA MEG3 has been demonstrated to suppress osteogenic differentiation; at the same time, lncRNA CCATI/ miR-148a and lncRNA LINC01133 have been shown to influence the process of proliferation in cases of osteosarcoma [10,11]. Studies have highlighted a correlation between the Notch signaling pathway and Haju-Cheney syndrome, a disorder that results in osteoporosis [12].…”

Section: Introductionmentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Osteoporosis is a commonly occurring condition marked by a loss of bone density. Previous evidence has highlighted the roles played by microRNAs as potential treatment tools for the disease. At present, the influence of long non-coding RNAs (lncRNAs) on the progression of osteoporosis remains largely unclear. Thus, an investigation was conducted into the target relationship between LINC00311, which has been reported to be highly expressed in osteoporosis, and delta-like 3 (DLL3), which is involved in the Notch signaling pathway, in connection with a series of bioinformatic methods. An osteoporotic rat model was established by means of ovariectomy (OVX) to evaluate the influence exerted by DLL3-binding LINC00311 on osteoclasts through the Notch signaling pathway. Methods: Osteoclasts were extracted from osteoporotic rats and transfected with the LINC00311-vector, shRNA-LINC00311, Notch activator, or a combination of the Notch activator and LINC00311-vector. Western blotting and RT-qPCR techniques were applied to determine the expression levels of LINC00311, DLL3, Notch1, Notch2, Jagged1, Hes-1 and TRAP in tissues and cells, while cell activity was detected by MTT assay. The cell cycle as well as the rate of apoptosis was detected by flow cytometry. The successfully established osteoporotic rats were designated into the OVX-siRNA, OVX-LINC00311 and OVX-control groups to observe the effects of LINC00311 on the proliferation and differentiation of osteoclasts. Results: Cells transfected with the LINC00311-vector exhibited increased expression levels of Notch2 and TRPA as well as increased cell activity, while decreased expression levels of DLL3, Notch1, Jagged1 and Hes-1, along with a decreased cell apoptosis rate, were observed. The opposite tendencies of these parameters were observed in the cells treated with shRNA-LINC00311. A key observation was made when the Notch signaling pathway was activated, in that the cell activity was decreased while the rate of apoptosis increased. In comparison with the OVX-control group, the expression levels of LINC00311, Notch2 and TRAP as well as the positive expression rate of TRAP all exhibited reductions, while those of DLL3, Jagged1 and Notch1 were elevated in the OVX-siRNA group. Compared with those in the sham group, in the OVX-control and OVX-LINC00311 groups, LINC00311 and the expression levels of Notch2 and TRAP were increased; however, decreased levels of DLL3, Jagged1 and Notch1 were noted. Conclusions: Taken together, the key findings of the present study suggest that LINC00311 induces proliferation and inhibits apoptosis of osteoclasts via the regulation of the Notch signaling pathway by inhibiting DLL3 expression, ultimately demonstrating that LINC00311 and its target gene DLL3 may serve as independent factors in cases of osteoporosis.

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Section: Introductionmentioning

confidence: 99%

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

Wang¹,

Luo²,

Liu³

et al. 2018

Cell Physiol Biochem

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“…LncRNAs play important roles in regulating cell differentiation, organ development, and diseases in eukaryotes. To date, many lncRNAs have been demonstrated to regulate osteogenic differentiation, including lncRNA MEG3, lncRNA TCONS_00041960, H19, and so on (B. Li et al, , ; Liao et al, ; Shang et al, ; Wu et al, ; Q. Wang et al, ). These substantiated that lncRNAs are critical elements in osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation

Chen

Wang

et al. 2019

Journal Cellular Physiology

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The incidence of postmenopausal osteoporosis research 50% in middle‐aged and older women, however, effects of existing therapy are not ideal. Emerging evidence have proved that long noncoding RNAs (lncRNAs) was correlated with multiple physiological and pathology processes including development, carcinogenesis, and osteogenesis. However, reports on lncRNAs regulating bone formation were relatively limited. In this study, we screened osteogenic lncRNAs through mRNA/lncRNA microarray combined with gene coexpression analysis. The biological function of the screened lncRNA was assessed both in vitro and in vivo. The effects of the lncRNA on osteogenic transcription factors were also evaluated. We identified AK016739, which was correlated with osteogenic differentiation and enriched in skeletal tissues of mice. The expression levels of AK016739 in bone‐derived mesenchymal stem cells were increased with age and negatively correlated with osteogenic differentiation marker genes. Experiments showed that AK016739 inhibited osteoblast differentiation, and in vivo inhibition of AK016739 by its small interfering RNA would rescue bone formation in ovariectomized osteoporosis mice model. In addition, AK016739 suppressed both expression levels and activities of osteogenic transcription factors. This newly identified lncRNA AK016739 has revealed a new mechanism of osteogenic differentiation and provided new targets for treatment of skeletal disorders.

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“…BALB/c mice (Beijing Vital River Laboratory Animal Technology Co., Ltd., Beijing, China) were divided into OVX model group ( n = 6) and sham operation group ( n = 6). The OVX mouse model was established as previously described (Q. Wang et al, ). Mice were anesthetized with 5% ketamine, and then the bilateral ovaries of mice were removed under aseptic conditions.…”

Section: Methodsmentioning

confidence: 99%

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

Zhou

Liu

et al. 2019

Journal Cellular Physiology

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Objective To investigate the mechanism of H19 on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs). Methods Ovariectomized (OVX) mouse model was established. RNA immunoprecipitation and RNA pull‐down assays were performed to determine the correlation between H19 and forkhead box C2 (Foxc2). Chromatin immunoprecipitation assay was used to identify whether Foxc2 binds to the Wnt4 promoter region. Molecules expressions were measured by quantitative real‐time polymerase chain reaction and western blot. Results We found that H19 expression was reduced in the serum of patients with postmenopausal osteoporosis and BMSCs of OVX mice, and overexpression of H19 promoted osteogenic differentiation of BMSCs. Additionally, Foxc2 could bind to the Wnt4 promoter and promote its transcription. We also showed that H19 could bind to Foxc2, and H19/Foxc2 regulated Wnt promoter expression in a synergistic fashion, and H19/Foxc2 regulated osteogenic differentiation of BMSCs through Wnt‐β‐catenin pathway. Conclusion H19 and Foxc2 synergistically promoted osteogenic differentiation of BMSCs via Wnt‐β‐catenin pathway.

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LncRNA MEG3 inhibited osteogenic differentiation of bone marrow mesenchymal stem cells from postmenopausal osteoporosis by targeting miR-133a-3p

Cited by 178 publications

References 20 publications

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

LncRNA LINC00311 Promotes the Proliferation and Differentiation of Osteoclasts in Osteoporotic Rats Through the Notch Signaling Pathway by Targeting DLL3

A novel long noncoding RNA AK016739 inhibits osteoblast differentiation and bone formation

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

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