LncRNA ENST00000563492 promoting the osteogenesis–angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p

Ouyang, Zhengxiao; Tan, Tingting; Zhang, Xianghong; Wan, Jia; Zhou, Yanling; Jiang, Guangyao; Yang, Daishui; Liu, Tang

doi:10.1038/s41419-020-2689-4

Cited by 35 publications

(30 citation statements)

References 38 publications

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“…More importantly, previous data have also documented that miR‐205‐5p works as an anti‐tumor miRNA to regulate the progression of PCa 19 . Meanwhile, it is also noteworthy that miR‐205‐5p bound by lncRNA ENST00000563492 has been shown to facilitate the osteogenesis in BMSCs 46 . Furthermore, our experimental findings demonstrated that NEAT1 inhibited miR‐205‐5p to promote the activity of ALP and mineralization of extracellular matrix and continuously upregulated the mRNA levels of RUNX2, ALP, COL1A1, and OCN, thereby contributing to osteogenic differentiation of hBMSCs and presenting a promising target for therapeutics through this axis.…”

Section: Discussionmentioning

confidence: 94%

LncRNA nuclear‐enriched abundant transcript 1 shuttled by prostate cancer cells‐secreted exosomes initiates osteoblastic phenotypes in the bone metastatic microenvironment via miR‐205‐5p/runt‐related transcription factor 2/splicing factor proline‐ and glutamine‐rich/polypyrimidine tract‐binding protein 2 axis

Huang

Liu

et al. 2021

Clinical & Translational Med

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Prostate cancer (PCa) patients commonly present with osteoblastic‐type bone metastasis. Exosomes derived from tumor cells possess biological significance and can mediate intercellular communication in the tumor microenvironment. Long noncoding RNA (lncRNA) nuclear‐enriched abundant transcript 1 (NEAT1) is also implicated in the stability in tumorigenesis and the development of PCa, but the underlying mechanism remains elusive. Hence, the current study set out to investigate the physiological mechanisms by which exosomes‐encapsulated NEAT1 affects the progression of PCa. First, after isolation, we found PCa cell‐derived exosomes induced the osteogenic differentiation of human bone marrow‐derived mesenchymal stem cells (hBMSCs). Besides, NEAT1 in PCa cells could be transferred into hBMSCs via exosomes. Further gain‐ and loss‐of‐function experimentation revealed that NEAT1 acted as a competing endogenous RNA (ceRNA) of microRNA (miR)‐205‐5p to upregulate the runt‐related transcription factor 2 (RUNX2) levels. Moreover, NEAT1 could promote the RUNX2 expression via the splicing factor proline‐ and glutamine‐rich (SFPQ)/polypyrimidine tract‐binding protein 2 (PTBP2) axis. Functional assays uncovered that NEAT1 shuttled by PCa‐exosomes facilitated the activity of alkaline phosphatase (ALP) and mineralization of extracellular matrix, and continuously upregulated the levels of RUNX2, ALP, alpha‐1 type 1 collagen, and osteocalcin by regulating RUNX2, to induce the osteogenic differentiation of hBMSCs. Furthermore, in vivo experimentation confirmed that upregulated NEAT1 induced osteogenesis. Collectively, our findings indicated that PCa‐derived exosomes‐loaded NEAT1 upregulated RUNX2 to facilitate the osteogenesis of hBMSCs by competitively binding to miR‐205‐5p via the SFPQ/PTBP2 axis, therefore providing a potential therapeutic target to treat osteogenesis of hBMSCs in PCa. PCa cells secrete exosomes containing NEAT1, and NEAT1 exerts effects on osteogenic differentiation of hBMSCs in PCa. NEAT1 shuttled by PCa‐derived exosomes could be transferred into hBMSCs, where NEAT1 exerted inductive properties in osteogenic differentiation of hBMSCs through the upregulation of RUNX2 by competitively binding to miR‐205‐5p and regulating SFPQ/PTBP2 in vitro and in vivo .

show abstract

Section: Discussionmentioning

confidence: 94%

LncRNA nuclear‐enriched abundant transcript 1 shuttled by prostate cancer cells‐secreted exosomes initiates osteoblastic phenotypes in the bone metastatic microenvironment via miR‐205‐5p/runt‐related transcription factor 2/splicing factor proline‐ and glutamine‐rich/polypyrimidine tract‐binding protein 2 axis

Huang

Liu

et al. 2021

Clinical & Translational Med

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“…During this process, the expression of VEGF improves the coupling process of osteogenesis and angiogenesis. 106 Studies have revealed that MIR22HG expression is significantly reduced in BMSCs of osteoporotic mice and upregulated in hBMSCs during osteogenic differentiation. 107 In addition, a considerable quantity of literatures have described MSCs have the abilities not only in osteogenic differentiation, but also in adipogenic, myogenic and chondrogenic differentiation.…”

Section: The Role Of Lncrnas In Osteogenesismentioning

confidence: 99%

LncRNAs as a new regulator of chronic musculoskeletal disorder

et al. 2021

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Musculoskeletal disorders are a group of conditions that affect the motor system, including bones, muscles, tendons, ligaments and joints. 1 People with multiple disorders are particularly vulnerable, especially in the context of an ageing population. Musculoskeletal disorders include a variety of conditions such as osteoarthritis (OA), rheumatoid arthritis (RA), osteopenia, osteoporosis, fractures, sarcopenia, etc. 2 Non-protein-coding RNA makes up 98% of the whole human genome. 3,4 These functional RNAs can be divided into two groups according to the threshold of 200 nucleotides (NTS): small and long non-coding RNAs (lncRNAs). 5,6 LncRNAs regulate the activities of both nearby and distant genes by multiple mechanisms. It could act as a scaffold for transcription factors and other molecules involved in transcription initiation. 7 Moreover, it could serve as protein and microRNA decoys to interfere with cell division by regulating a series of key genes. 8 For those mainly located in the cytoplasm, it could directly target mRNA and induce translation. 9 Currently, an increased number of lncRNAs are found to be involved in the regulation of development and homeostasis of skeletal muscle system. 10,11 It is notable that lncRNAs take key roles in musculoskeletal disorders.

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“…Currently, stem cell-based tissue engineering reconstruction of bone defect is a feasible and continuously developing strategy to restore structure and function [3]. Bone marrow mesenchymal stem cells (BMSCs), a seed of bone regeneration, can differentiate into osteoblasts and secrete angiogenic factors to promote bone regeneration [4][5][6]. Thus, the BMSCs have potential to couple the osteogenesis and angiogenesis processes.…”

Section: Introductionmentioning

confidence: 99%

Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways

Tan

Zhou

Zheng

et al. 2021

Stem Cells International

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The combination of osteogenesis and angiogenesis dual-delivery trace element-carrying bioactive scaffolds and stem cells is a promising method for bone regeneration and repair. Canonical Wnt and HIF-1α signaling pathways are vital for BMSCs’ osteogenic differentiation and secretion of osteogenic factors, respectively. Simultaneously, lithium (Li) and copper (Cu) can activate the canonical Wnt and HIF-1α signaling pathway, respectively. Moreover, emerging evidence has shown that the canonical Wnt and HIF signaling pathways are related to coupling osteogenesis and angiogenesis. However, it is still unclear whether the lithium- and copper-doped bioactive scaffold can induce the coupling of the osteogenesis and angiogenesis in BMSCs and the underlying mechanism. So, we fabricated a lithium- (Li+-) and copper- (Cu2+-) doped organic/inorganic (Li 2.5-Cu 1.0-HA/Col) scaffold to evaluate the coupling osteogenesis and angiogenesis effects of lithium and copper on BMSCs and further explore its mechanism. We investigated that the sustained release of lithium and copper from the Li 2.5-Cu 1.0-HA/Col scaffold could couple the osteogenesis- and angiogenesis-related factor secretion in BMSCs seeding on it. Moreover, our results showed that 500 μM Li+ could activate the canonical Wnt signaling pathway and rescue the XAV-939 inhibition on it. In addition, we demonstrated that the 25 μM Cu2+ was similar to 1% oxygen environment in terms of the effectiveness of activating the HIF-1α signaling pathway. More importantly, the combination stimuli of Li+ and Cu2+ could couple the osteogenesis and angiogenesis process and further upregulate the osteogenesis- and angiogenesis-related gene expression via crosstalk between the canonical Wnt and HIF-1α signaling pathway. In conclusion, this study revealed that lithium and copper could crosstalk between the canonical Wnt and HIF-1α signaling pathways to couple the osteogenesis and angiogenesis in BMSCs when they are sustainably released from the Li-Cu-HA/Col scaffold.

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LncRNA ENST00000563492 promoting the osteogenesis–angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by functions as a ceRNA for miR-205-5p

Cited by 35 publications

References 38 publications

LncRNAs as a new regulator of chronic musculoskeletal disorder

Lithium and Copper Induce the Osteogenesis-Angiogenesis Coupling of Bone Marrow Mesenchymal Stem Cells via Crosstalk between Canonical Wnt and HIF-1α Signaling Pathways

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