Osteogenic differentiation of rat bone mesenchymal stem cells modulated by MiR-186 via SIRT6

Xiao, Jijie; Qin, Sisi; Li, Wei; Lin, Yu; Huang, Pan-Hui; Liao, Jianwei; Liu, Jue; Li, Shaolin

doi:10.1016/j.lfs.2020.117660

Cited by 20 publications

(10 citation statements)

References 21 publications

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“…Similarly, SIRT6 has a therapeutic effect on periapical lesions through suppression of chemokine (C-C motif) ligand 2 (CCL2) synthesis [19]. However, Xiao et al indicated that SIRT6 have an inhibitory effect on osteogenic differentiation of BMSCs [20]. In our study, we found overexpression of SIRT6 attenuates the inhibitory effect of miR-545-3p on osteoblasts.…”

Section: Discussionmentioning

confidence: 49%

MiR-545-3p Upregulated in Osteoporosis and Regulates The Apoptosis of Osteoblasts by Targeting SIRT6

Pei

et al. 2020

Preprint

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Background: The imbalance of proliferation and apoptosis plays an important role in the pathogenesis of osteoporosis. MicroRNAs play an important role in the apoptosis of osteoblasts cells. However, the role and potential mechanism of miR-545-3p in regulating osteoblast apoptosis remain unclear. The purpose of this study was to investigate the effect of miR-545-3p on osteoblast cells apoptosis and explore the mechanism of osteoporosis.Methods: Osteogenic medium was used to induce the differentiation of osteoblasts MC3T3-E1 to construct the osteoporosis model, and the expression of ALP, Runx2, OCN were detected by western blot; miR-545-3p mRNA was detected by RT-PCR. Transfected with miR-545-3p mimics into MC3T3-E1, then flow cytometry was used to detected the changes of apoptosis status. The expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot. Bioinformatics was used to analyze the binding protein of miR-545-3p, and luciferase reporter gene experiment was used to verify whether miR-545-3p directly targets SIRT6; RT-qPCR and western blot were used to detect the expression level of SIRT6 after transfection of miR-545-3p mimics or miR-545-3p inhibitor. After co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6, the apoptosis status of osteoblasts was analyzed by flow cytometry, and the expression of apoptosis related proteins Bcl-2 and Bax were detected by western blot.Results: The expression of miR-545-3p in patients with osteoporosis was significantly higher than that of normal in GEO database (P<0.05). After osteoblasts were cultured in osteogenic medium, the expression of ALP, Runx2 and OCN was increased, and the expression of miR-545-3p was decreased. Flow cytometry analysis showed that overexpression of miR-545-3p promoted the apoptosis of osteoblasts. Western blot results showed that overexpression of miR-545-3p promoted the expression of Bax and decreased the expression of Bcl-2. Bioinformatics analysis showed that miR-545-3p could target SIRT6. The results of real-time PCR and western blot showed that SIRT6 expression was significantly inhibited by miR-545-3p mimics (P<0.05). Luciferase reporter gene assay showed that miR-545-3p significantly inhibited luciferase activity of wild-type SIRT6-3'UTR plasmid transfected cells (P<0.05), but had no effect on luciferase activity of mutant SIRT6-3'UTR plasmid transfected cells (P<0.05). However, co-transfection of miR-545-3p mimics and pcDNA3.1-SIRT6 could reduce the apoptosis, and western blot results showed that co-transfection promoted the expression of Bcl-2 and decreased the expression of Bax.Conclusions: miR-545-3p can promote the apoptosis of osteoblasts by inhibiting the expression of SIRT6, which provides a certain idea for the treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 49%

MiR-545-3p Upregulated in Osteoporosis and Regulates The Apoptosis of Osteoblasts by Targeting SIRT6

Pei

et al. 2020

Preprint

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“…For researchers, with the continuous development of research, the molecular mechanism of osteogenesis and adipogenesis of MSCs will be more distinct. The positive and negative feedback and bidirectional regulation of miRNAs on transcription factors and proteins has been demonstrated to be related to osteogenic and adipogenic differentiation of MSCs [18][19][20][21][22][23], and the effect of miRNA gene therapy targets for OP has significant potential. Most studies have demonstrated the ability of miRNAs to promote osteogenic differentiation of MSCs, and the significant effects thereof.…”

Section: Discussionmentioning

confidence: 99%

Current status and development trend of miRNAs in osteoporosis-related research: A bibliometric analysis

Wang

Pan

et al. 2021

Folia Histochem Cytobiol.

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“…Interestingly, an interaction between Sirt6 and NF-κB was observed in which Sirt6 downregulation by miR-186 resulted in enhanced phosphorylation of NF-κB. Therefore, miR-186 attenuated osteogenic differentiation by targeting Sirt6 and thereby upregulating NF-κB (159). An interesting miRNA, showing age dependent expression, is miR-188.…”

Section: Osteogenesis and Osteoblastogenesismentioning

confidence: 99%

miRNAs Related to Different Processes of Fracture Healing: An Integrative Overview

et al. 2021

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Fracture healing is a complex, dynamic process that is directed by cellular communication and requires multiple cell types, such as osteoblasts, osteoclasts, and immune cells. Physiological fracture healing can be divided into several phases that consist of different processes, such as angiogenesis, osteogenesis, and bone resorption/remodelling. This is needed to guarantee proper bone regeneration after fracture. Communication and molecular regulation between different cell types and within cells is therefore key in successfully orchestrating these processes to ensure adequate bone healing. Among others, microRNAs (miRNAs) play an important role in cellular communication. microRNAs are small, non-coding RNA molecules of ~22 nucleotides long that can greatly influence gene expression by post-transcriptional regulation. Over the course of the past decade, more insights have been gained in the field of miRNAs and their role in cellular signalling in both inter- and intracellular pathways. The interplay between miRNAs and their mRNA targets, and the effect thereof on different processes and aspects within fracture healing, have shown to be interesting research topics with possible future diagnostic and therapeutic potential. Considering bone regeneration, research moreover focusses on specific microRNAs and their involvement in individual pathways. However, it is required to combine these data to gain more understanding on the effects of miRNAs in the dynamic process of fracture healing, and to enhance their translational application in research, as well as in the clinic. Therefore, this review aims to provide an integrative overview on miRNAs in fracture healing, related to several key aspects in the fracture healing cascade. A special focus will be put on hypoxia, angiogenesis, bone resorption, osteoclastogenesis, mineralization, osteogenesis, osteoblastogenesis, osteocytogenesis, and chondrogenesis.

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Osteogenic differentiation of rat bone mesenchymal stem cells modulated by MiR-186 via SIRT6

Cited by 20 publications

References 21 publications

MiR-545-3p Upregulated in Osteoporosis and Regulates The Apoptosis of Osteoblasts by Targeting SIRT6

MiR-545-3p Upregulated in Osteoporosis and Regulates The Apoptosis of Osteoblasts by Targeting SIRT6

Current status and development trend of miRNAs in osteoporosis-related research: A bibliometric analysis

miRNAs Related to Different Processes of Fracture Healing: An Integrative Overview

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