Non-coding RNAs regulate the BMP/Smad pathway during osteogenic differentiation of stem cells

Zhang, Qiuling; Long, Yifei; Jin, Liangyu; Li, Chenghao; Long, Jie

doi:10.1016/j.acthis.2023.151998

Cited by 8 publications

(3 citation statements)

References 94 publications

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“…Our previous study has found that the miRNA-140-5p expression decreased during osteogenic differentiation process of BMSCs, and BMSCs osteogenic differentiation is promoted by miRNA-140-5p down-regulation through targeting the Wnt l signal pathway [7] , however, the relative mechanism about miRNA-140-5p low expression in this process is still unclear. LncRNAs, as a miRNA molecular sponge, LncRNAs have increasingly been studied in relation to osteogenic differentiation [24][25][26][27][28] . The predicted results of Star base Database indicated that lncRNA-H19 may target the miRNA-140-5p.…”

Section: Resultsmentioning

confidence: 99%

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

Liu,

Wang,

Zhang

et al. 2023

IJPS

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To explore the influence of the long-non coding RNA-H19/microRNA-140-5p/Wnt1 axis on the osteogenic differentiation in bone marrow mesenchymal stem cells. First, we used dual-luciferase reporter gene detection to verify long-non coding-H19/miRNA-140-5p/Wnt1 regulatory axis targeting relationship. Then long-non coding-H19 was overexpressed or silenced in bone marrow mesenchymal stem cells and then long-non coding-H19, microRNA-140-5p and Wnt1 expression were assessed using quantitative real-time polymerase chain reaction and cell activity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide. Then the osteogenic differentiation culture was performed, formation of calcium nodules were assessed via Alizarin red staining, while the expression of osteocalcin and runt-related transcription factor 2 detected via Western blot. Wild type long-non coding RNA-H19 group and wild type-Wnt1 group showed significantly decreased luciferase activity in dual-luciferase reporter assays (p<0.05). After overexpressed long-non coding RNA-H19, the microRNA-140-5p expression decreased and Wnt1 expression increased (p<0.05), and while silenced the long-non coding RNA-H19 expression, the opposite result was found (p<0.05). In terms of cell viability, there were no significant differences between groups after long-non coding RNA-H19 was overexpressed or silenced (p>0.05). After overexpressed long-non coding RNA-H19, calcium nodules formation, mineralized bone matrix level, the expression of osteocalcin and runt-related transcription factor 2 protein significantly increased (p<0.05), and while silenced the long-non coding RNA-H19 expression, the opposite result was found (p<0.05). Long-non coding RNA-H19 overexpression promotes the bone marrow mesenchymal stem cells osteogenic differentiation via targeting microRNA-140-5p/Wnt1 signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

Liu,

Wang,

Zhang

et al. 2023

IJPS

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“…The osteoblast differentiation process involves the regulation of gene expression, osteoblast differentiation marker genes, and mineral deposition [ 7 – 9 ]. Currently, many miRNAs emphasize great roles in skeletal development and homeostasis, especially in osteoblast differentiation [ 27 – 29 ]. Therefore, our study investigated miR-877-5p in osteoblast differentiation from the perspective of gene regulation and concluded that miR-877-5p promotes osteoblast differentiation by negatively regulating EIF4G2 expression.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression

Shen,

Zhang,

Wang

et al. 2024

J Orthop Surg Res

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Stimulating bone formation potentially suggests therapeutics for orthopedic diseases including osteoporosis and osteoarthritis. Osteoblasts are key to bone remodeling because they act as the only bone-forming cells. miR-877-5p has a chondrocyte-improving function in osteoarthritis, but its effect on osteoblast differentiation is unknown. Here, miR-877-5p-mediated osteoblast differentiation was studied. Real-time reverse transcriptase-polymerase chain reaction was performed to measure miR-877-5p expression during the osteogenic differentiation of MC3T3-E1 cells. Osteoblast markers, including alkaline phosphatase (ALP), collagen type I a1 chain, and osteopontin, were measured and detected by alizarin red staining and ALP staining. Potential targets of miR-877-5p were predicted from three different algorithms: starBase (http://starbase.sysu.edu.cn/), PITA (http://genie.weizmann.ac.il/pubs/mir07/mir07_data.html), and miRanda (http://www.microrna.org/microrna/home.do). It was further verified by dual luciferase reporter gene assay. The experimental results found that miR-877-5p was upregulated during the osteogenic differentiation of MC3T3-E1 cells. Overexpression of miR-877-5p promoted osteogenic differentiation, which was characterized by increased cell mineralization, ALP activity, and osteogenesis-related gene expression. Knockdown of miR-877-5p produced the opposite result. Dual luciferase reporter gene assay showed that miR-877-5p directly targeted eukaryotic translation initiation factor 4γ2 (EIF4G2). Overexpression of EIF4G2 inhibited osteogenic differentiation and reversed the promoting effect of overexpression of miR-135-5p on osteogenic differentiation. These results indicate that miR-877-5p might have a therapeutic application related to its promotion of bone formation through targeting EIF4G2.

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“…NcRNAs are primarily encoded by genes without protein-coding capability as they do not undergo the canonical post-transcriptional mRNA modification/translational processes [2][3][4]. These molecules are classified into long and small ncRNAs (lncRNAs/sncRNAs) [5][6][7]. The first group has recently emerged as a regulator of numerous pathways and cell processes [1,[8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

Mazziotta,

Badiale,

Cervellera

et al. 2024

Theranostics

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Human osteogenic differentiation is a complex and well-orchestrated process which involves a plethora of molecular players and cellular processes. A growing number of studies have underlined that circular RNAs (circRNAs) play an important regulatory role during human osteogenic differentiation. CircRNAs are single-stranded, covalently closed non-coding RNA molecules that are acquiring increased attention as epigenetic regulators of gene expression. Given their intrinsic high conformational stability, abundance, and specificity, circRNAs can undertake various biological activities in order to regulate multiple cellular processes, including osteogenic differentiation. The most recent evidence indicates that circRNAs control human osteogenesis by preventing the inhibitory activity of miRNAs on their downstream target genes, using a competitive endogenous RNA mechanism. The aim of this review is to draw attention to the currently known regulatory mechanisms of circRNAs during human osteogenic differentiation. Specifically, we provide an understanding of recent advances in research conducted on various human mesenchymal stem cell types that underlined the importance of circRNAs in regulating osteogenesis. A comprehensive understanding of the underlying regulatory mechanisms of circRNA in osteogenesis will improve knowledge on the molecular processes of bone growth, resulting in the potential development of novel preclinical and clinical studies and the discovery of novel diagnostic and therapeutic tools for bone disorders.

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Non-coding RNAs regulate the BMP/Smad pathway during osteogenic differentiation of stem cells

Cited by 8 publications

References 94 publications

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

Long Non-coding RNA-H19 Regulates Osteogenic Differentiation via microRNA-140-5p/Wnt1 Signaling in Bone Marrow Mesenchymal Stem Cells

MicroRNA-877-5p promotes osteoblast differentiation by targeting EIF4G2 expression

Regulatory mechanisms of circular RNAs during human mesenchymal stem cell osteogenic differentiation

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