LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions

Zhou, Xiaozhong; Xu, Wangyang; Wang, Yeyang; Zhang, Hui; Zhang, Li; Li, Chao; Yao, Shun; Huang, Zixiang; Huang, Lijuan; Luo, Dan

doi:10.1186/s11658-021-00269-6

Cited by 24 publications

(8 citation statements)

References 49 publications

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“…These data showed that miR-127-5p might exert a regulative role on osteogenesis by modulating multiple pathways. In line with this hypothesis, several negative regulators of osteogenesis has been identified as the target for miR-127-5p, like Gremlin2 [ 26 ], which is a bone morphogenetic protein antagonists and suppresses osteogenesis in BMSCs [ 27 ], and PTEN [ 25 ]. Further study is warranted to reveal other mechanisms underlying the regulation of miR-127-5p in osteogenesis.…”

Section: Discussionmentioning

confidence: 99%

Circ_0134944 inhibits osteogenesis through miR-127-5p/PDX1/SPHK1 pathway

Zhang

Chen

et al. 2021

Regenerative Therapy

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Introduction Osteoporosis, a common skeletal disorder mainly affecting postmenopausal women, is characterized by the imbalance between osteogenesis and osteoclastogenesis. Circ_0134944 has been recently found to be upregulated in postmenopausal osteoporosis (PMOP) patients. However, its role in osteogenesis remains unknown. Here we aimed to explore the role of circ_0134944 in osteogenesis and reveal the underlying mechanism. Methods qRT-PCR was used to determine the expression of circ_0134944, miR-127-5p, PDX1 and SPHK1 in the blood mononuclear cells (BMCs) of PMOP patients. Bone marrow mesenchymal stem cells (BMSCs) were used as the cellular model. Western blotting and qRT-PCR were used to determine the expression of osteogenesis-related genes (Runx2, OPN, OCN). ALP and Alizarin Red S staining were performed to evaluate osteogenic differentiation. The interactions between circ_0134944 and miR-127-5p, miR-127-5p and PDX1, PDX1 and SPHK1 were determined by dual-luciferase reporter and ChIP assay. Results Circ_0134944, PDX1 and SPHK1 were upregulated while miR-127-5p was downregulated in PMOP patients. Enhanced expression of circ_0134944 suppressed osteogenesis, which was then reversed by miR-127-5p overexpression. The binding between circ_0134944 and miR-127-5p, PDX1 and miR-127-5p were confirmed by dual-luciferase reporter assay. Moreover, PDX1 was enriched in the promoter region of SPHK1, and SPHK1 overexpression prevented the promotion of osteogenesis induced by miR-127-5p overexpression. Conclusions Taken together, these results demonstrate that circ_0134944 inhibit osteogenesis via miR-127-5p/PDX1/SPHK1 axis. Thus, the present study offered evidence that circ_0134944/miR-127-5p/PDX1/SPHK1 axis could be a potential therapeutic target for PMOP.

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Section: Discussionmentioning

confidence: 99%

Circ_0134944 inhibits osteogenesis through miR-127-5p/PDX1/SPHK1 pathway

Zhang

Chen

et al. 2021

Regenerative Therapy

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“…The migration and viability of MSCs was promoted by P21 under in vitro hypoxic preconditioning (79). DNM3OS/miR-127-5p /GREM2 may be involved in hypoxic chondrocyte differentiation (95). H19 enhanced the survival rate and angiogenesis potential of BMSCs in vitro.…”

Section: Hypoxia Induced Ncrnas With a Role In The Fate Of Mscsmentioning

confidence: 95%

Hypoxia-Inducible Non-coding RNAs in Mesenchymal Stem Cell Fate and Regeneration

Zhao

et al. 2021

Front. Dent. Med

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Mesenchymal stem cells (MSCs) can differentiate into multiple cell lines, which makes them an important source of cells for tissue engineering applications. They are defined by the capability to renew themselves and maintain pluripotency. This ability is modulated by the balance between complex cues from cellular microenvironment. Self-renewal and differentiation abilities are regulated by particular microenvironmental signals. Oxygen is considered to be an important part of cell microenvironment, which not only acts as a metabolic substrate but also a signal molecule. It has been proved that MSCs are hypoxic in the physiological environment. Signals from MSCs' microenvironment or niche which means the anatomical location of the MSCs, maintain the final properties of MSCs. Physiological conditions like oxygen tension are deemed to be a significant part of the mesenchymal stem cell niche, and have been proved to be involved in modulating embryonic and adult MSCs. Non-coding RNAs (ncRNAs), which play a key role in cell signal transduction, transcription and translation of genes, have been widely concerned as epigenetic regulators in a great deal of tissues. With the rapid development of bioinformatics analysis tools and high-throughput RNA sequencing technology, more and more evidences show that ncRNAs play a key role in tissue regeneration. It shows potential as a biomarker of MSC differentiation. In this paper, we reviewed the physiological correlation of hypoxia as a unique environmental parameter which is conducive to MSC expansion and maintenance, discussed the correlation of tissue engineering, and summarized the influence of hypoxia related ncRNAs on MSCs' fate and regeneration. This review will provide reference for future research of MSCs' regeneration.

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“…Rat MSCs have been widely explored due to their capability to regenerate and differentiate to more specialized cells, including bone cells (osteocytes), fat cells (adipocytes) and cartilage cells (chondrocytes) [140]. Bone marrow highly enables the isolation of these cells, which is mostly obtained from rat femur and tibia parts [141].…”

Section: Graphene Oxide In Rat Mesenchymal Stem Cellsmentioning

confidence: 99%

Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

et al. 2022

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Thanks to stem cells’ capability to differentiate into multiple cell types, damaged human tissues and organs can be rapidly well-repaired. Therefore, their applicability in the emerging field of regenerative medicine can be further expanded, serving as a promising multifunctional tool for tissue engineering, treatments for various diseases, and other biomedical applications as well. However, the differentiation and survival of the stem cells into specific lineages is crucial to be exclusively controlled. In this frame, growth factors and chemical agents are utilized to stimulate and adjust proliferation and differentiation of the stem cells, although challenges related with degradation, side effects, and high cost should be overcome. Owing to their unique physicochemical and biological properties, graphene-based nanomaterials have been widely used as scaffolds to manipulate stem cell growth and differentiation potential. Herein, we provide the most recent research progress in mesenchymal stem cells (MSCs) growth, differentiation and function utilizing graphene derivatives as extracellular scaffolds. The interaction of graphene derivatives in human and rat MSCs has been also evaluated. Graphene-based nanomaterials are biocompatible, exhibiting a great potential applicability in stem-cell-mediated regenerative medicine as they may promote the behaviour control of the stem cells. Finally, the challenges, prospects and future trends in the field are discussed.

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LncRNA DNM3OS regulates GREM2 via miR-127-5p to suppress early chondrogenic differentiation of rat mesenchymal stem cells under hypoxic conditions

Cited by 24 publications

References 49 publications

Circ_0134944 inhibits osteogenesis through miR-127-5p/PDX1/SPHK1 pathway

Circ_0134944 inhibits osteogenesis through miR-127-5p/PDX1/SPHK1 pathway

Hypoxia-Inducible Non-coding RNAs in Mesenchymal Stem Cell Fate and Regeneration

Impact of Graphene Derivatives as Artificial Extracellular Matrices on Mesenchymal Stem Cells

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