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

Gan, Xiaoliang; Liu, Shuaibin; Liang, Kunneng

doi:10.1186/s12881-020-0948-y

Cited by 45 publications

(37 citation statements)

References 31 publications

(32 reference statements)

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“…Our results were consistent with Zeng et al [22]. H19 plays a critical role in the differentiation of many vital organs and plays pivotal roles in the differentiation of mesenchymal stem cells [23][24][25][26]. Keniry et al [27] found that H19 can enhance the expression level of RUNX2 to promote bone regeneration.…”

Section: Discussionsupporting

confidence: 92%

LncRNA H19 promotes odontoblastic differentiation of human dental pulp stem cells by regulating miR-140-5p and BMP-2/FGF9

Zhong

Kong

et al. 2020

Stem Cell Res Ther

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Background Increasing evidence has revealed that long non-coding RNAs (lncRNAs) exert critical roles in biological mineralization. As a critical process for dentin formation, odontoblastic differentiation is regulated by complex signaling networks. The present study aimed to investigate the biological role and regulatory mechanisms of lncRNA-H19 (H19) in regulating the odontoblastic differentiation of human dental pulp stem cells (hDPSCs). Methods We performed lncRNA microarray assay to reveal the expression patterns of lncRNAs involved in odontoblastic differentiation. H19 was identified and verified as a critical factor by qRT-PCR. The gain- and loss-of-function studies were performed to investigate the biological role of H19 in regulating odontoblastic differentiation of hDPSCs in vitro and in vivo. Odontoblastic differentiation was evaluated through qRT-PCR, Western blot, and Alizarin Red S staining. Bioinformatics analysis identified that H19 could directly interact with miR-140-5p, which was further verified by luciferase reporter assay. After overexpression of miR-140-5p in hDPSCs, odontoblastic differentiation was determined. Moreover, the potential target genes of miR-140-5p were investigated and the biological functions of BMP-2 and FGF9 in hDPSCs were verified. Co-transfection experiments were conducted to validate miR-140-5p was involved in H19-mediated odontoblastic differentiation in hDPSCs. Results The expression of H19 was significantly upregulated in hDPSCs undergoing odontoblastic differentiation. Overexpression of H19 stimulated odontoblastic differentiation in vitro and in vivo, whereas downregulation of H19 revealed the opposite effect. H19 binds directly to miR-140-5p and overexpression of miR-140-5p inhibited odontoblastic differentiation of hDPSCs. H19 acted as a miR-140-5p sponge, resulting in regulated the expression of BMP-2 and FGF9. Overexpression of H19 abrogated the inhibitory effect of miR-140-5p on odontoblastic differentiation. Conclusion Our data revealed that H19 plays a positive regulatory role in odontoblastic differentiation of hDPSCs through miR-140-5p/BMP-2/FGF9 axis, suggesting that H19 may be a stimulatory regulator of odontogenesis.

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“…For instance, Fan et al identi ed that miR-532-3p attenuated osteogenic differentiation by downregulating ETS1 [23]. Gan et al reported that miR-19b-3p promoted osteogenic differentiation of BMSCs [24]. In our study, miR-374a was predicted as a potential target of LINC00899, and dual-luciferase reporter and RIP assays veri ed the interaction.…”

Section: Discussionsupporting

confidence: 63%

LINC00899 Promotes Osteogenic Differentiation and Alleviates Osteoporosis via Targeting miR-374a to Regulate RUNX2

Gao

Xue

Yang

2020

Preprint

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Objective: This study aims to illustrate the underlying molecular mechanisms of long noncoding RNAs (LncRNAs) LINC00899 in osteoporosis.Methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) used to examine the levels of LINC00899, miR-374a and RUNX2 in clinical tissues or human bone mesenchymal stem cells (hBMSCs). The interaction between miR-374a and LINC00899 or RUNX2 was predicted by starBase and verified by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. Results: The expression of LINC00899 was lowly expressed in osteoporotic patients’ bone tissues and knockdown of LINC00899 decreased the expression of osteogenesis-related genes. Moreover, LINC00899 was confirmed to inhibit miR-374a expression by direct interaction. the expression levels of LINC00899 were gradually increased, but miR-374a expression was decreased with the prolongation of osteogenic induction. Finally, we demonstrated that RUNX2 was a target of miR-374a, and the silencing of miR-374a partially abolished the inhibitory effect of LINC00899 knockdown on the expression of RUNX2, OPN and OCN.Conclusions: We demonstrated that LINC00899 facilitated osteogenic differentiation of hBMSCs and prevent osteoporosis by sponging miR-374a and enhancing RUNX2 expression, which might provide a useful therapeutic strategy for osteoporosis patients.

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“…For instance, Fan et al identi ed that miR-532-3p attenuated osteogenic differentiation by downregulating ETS1 [28]. Gan et al reported that miR-19b-3p promoted osteogenic differentiation of BMSCs [29]. In our study, miR-374a was predicted as a potential target of LINC00899, and dual-luciferase reporter and RIP assays veri ed the interaction.…”

Section: Discussionsupporting

confidence: 63%

LINC00899 promotes osteogenic differentiation and alleviates osteoporosis via targeting miR-374a to regulate RUNX2

Gao

Xue

Yang

2020

Preprint

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Objective: This study aims to illustrate the underlying molecular mechanisms of long noncoding RNAs (LncRNAs) LINC00899 in osteoporosis.Methods: Real Time-quantitative Polymerase Chain Reaction (RT-qPCR) was used to examine the levels of LINC00899, miR-374a and RUNX2 in clinical tissues or human bone mesenchymal stem cells (hBMSCs). The interaction between miR-374a and LINC00899 or RUNX2 was predicted by starBase and verified by luciferase reporter assay and RNA binding protein immunoprecipitation (RIP) assay. Alkaline phosphatase (ALP) activity and Alizarin Red S (ARS) staining were also used to evaluate the osteogenic ability of hBMSCs.Results: The expression levels of LINC00899 were gradually increased, but miR-374a expression was decreased with the prolongation of osteogenic induction. In addition, the expression of LINC00899 was lowly expressed in osteoporotic patients’ bone tissues and knockdown of LINC00899 decreased the expression of osteogenesis-related genes. Moreover, LINC00899 was confirmed to inhibit miR-374a expression by direct interaction. Finally, we demonstrated that RUNX2 was a target of miR-374a, and the silencing of miR-374a partially abolished the inhibitory effect of LINC00899 knockdown on the expression of RUNX2, OPN and OCN.Conclusions: We demonstrated that LINC00899 facilitated the osteogenic differentiation of hBMSCs and prevented osteoporosis by sponging miR-374a and enhancing RUNX2 expression, which might provide a useful therapeutic strategy for osteoporosis patients.

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“…In the last of three studies on the role of lncRNA H19 in osteogenesis, Xiaoling et al [70] investigated the serum expression levels of miR-19b-3p and lncRNA H19 between 18 osteoporotic patients and 12 HC, and their effects on osteoblast proliferation and differentiation of BMP-2-induced hBMSCs. Serum expression levels of miR-19b-3p resulted to be elevated, while those of H19 resulted to be downregulated in osteoporotic patients compared to the control group.…”

Section: Lncrnas As Negative Regulatorsmentioning

confidence: 99%

The Involvement of Long Non-Coding RNAs in Bone

Aurilia

Donati

Palmini

et al. 2021

IJMS

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A harmonious balance between osteoblast and osteoclast activity guarantees optimal bone formation and resorption, pathological conditions affecting the bone may arise. In recent years, emerging evidence has shown that epigenetic mechanisms play an important role during osteoblastogenesis and osteoclastogenesis processes, including long non-coding RNAs (lncRNAs). These molecules are a class of ncRNAs with lengths exceeding 200 nucleotides not translated into protein, that have attracted the attention of the scientific community as potential biomarkers to use for the future development of novel diagnostic and therapeutic approaches for several pathologies, including bone diseases. This review aims to provide an overview of the lncRNAs and their possible molecular mechanisms in the osteoblastogenesis and osteoclastogenesis processes. The deregulation of their expression profiles in common diseases associated with an altered bone turnover is also described. In perspective, lncRNAs could be considered potential innovative molecular biomarkers to help with earlier diagnosis of bone metabolism-related disorders and for the development of new therapeutic strategies.

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“…For example, lncRNA-H19 inhibits MSC proliferation and osteogenic differentiation via suppressing miR-196-3p when estrogen exists. However, in postmenopausal osteoporosis, H19 expression level decreases [ 121 ]. Similarly, in ONFH, lncRNA-HOTAIR is upregulated and promotes osteogenesis via the miR-17-5p/Smad7 pathway [ 122 ].…”

Section: Epigenetic Regulation In Msc Aging and Osteoporosismentioning

confidence: 99%

Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

Wang

Zhu

et al. 2020

Stem Cells International

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Mesenchymal stem cells (MSCs) are a reliable source for cell-based regenerative medicine owing to their multipotency and biological functions. However, aging-induced systemic homeostasis disorders in vivo and cell culture passaging in vitro induce a functional decline of MSCs, switching MSCs to a senescent status with impaired self-renewal capacity and biased differentiation tendency. MSC functional decline accounts for the pathogenesis of many diseases and, more importantly, limits the large-scale applications of MSCs in regenerative medicine. Growing evidence implies that epigenetic mechanisms are a critical regulator of the differentiation programs for cell fate and are subject to changes during aging. Thus, we here review epigenetic dysregulations that contribute to MSC aging and osteoporosis. Comprehending detailed epigenetic mechanisms could provide us with a novel horizon for dissecting MSC-related pathogenesis and further optimizing MSC-mediated regenerative therapies.

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

Cited by 45 publications

References 31 publications

LncRNA H19 promotes odontoblastic differentiation of human dental pulp stem cells by regulating miR-140-5p and BMP-2/FGF9

LINC00899 Promotes Osteogenic Differentiation and Alleviates Osteoporosis via Targeting miR-374a to Regulate RUNX2

LINC00899 promotes osteogenic differentiation and alleviates osteoporosis via targeting miR-374a to regulate RUNX2

The Involvement of Long Non-Coding RNAs in Bone

Epigenetic Regulation in Mesenchymal Stem Cell Aging and Differentiation and Osteoporosis

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